Sample records for caspases evolutionary aspects

  1. Theoretical Aspects of Evolutionary Algorithms

    Wegener, Ingo


    Randomized search heuristics like simulated annealing and evolutionary algorithms are applied successfully in many different situations. However, the theory on these algorithms is still in its infancy. Here it is discussed how and why such a theory should be developed. Afterwards, some fundamental results on evolutionary algorithms are presented in order to show how theoretical results on randomized search heuristics can be proved and how they contribute to the understanding of evolutionary a...

  2. Two Aspects of Evolutionary Algorithms


    In this paper we discuss the paradigm of evolutionary algorithms (Eas). We argue about the need for new heuristics in real-world problem solving, discussing reasons why some problems are difficult tosolve. After introducing the main concepts of evolutionary algorithms, we concentrate on two issues:(1)self-adaptation of the parameters of EA, and (2) handling constraints.

  3. Evolutionary aspects of love and empathy

    Allott, Robin


    Love has always been a central preoccupation in individual human lives, but there has been little consideration of it by psychologists or other scientists and little attempt to explain it as an evolutionary phenomenon. There are various possible behavioral precursors of love: animal "love", empathy, group feeling, sexuality, the mother/infant bond. The principal candidates are sexuality and the mother/infant bond. Sexuality has been favored as an origin by those few writers who have discussed...




    Full Text Available Interpersonal Attraction is the attraction between two people, which leads to friendships and even romantic relationships. Although Interpersonal Attraction has been a long - standing concept, only recently it is being studied regarding its neurobiological and socio evolutionary basis. It is now a major area of research in Social as well as Evolutionary Psychology.


    Smrithi; Devdas; Ashok; Meghashree; Aarathi


    Interpersonal Attraction is the attraction between two people, which leads to friendships and even romantic relationships. Although Interpersonal Attraction has been a long - standing concept, only recently it is being studied regarding its neurobiological and socio evolutionary basis. It is now a major area of research in Social as well as Evolutionary Psychology.

  6. Evolutionary aspects of gift-giving dynamics among Norwegian students


    Data from questionnaires filled out by 336 students during a nine day period in January and February 1999 at the University of Oslo, Norway was analyzed to find patterns in gift-giving behavior corresponding to predicted evolutionary biological and evolutionary psychological hypotheses. Gifts given and received, people given to and received from, monetary value of gifts given and estimated monetary value of gifts received were tallied. We tested the effects of four main factors: kin and non-k...

  7. Evolutionary aspects of life forms in angiosperm families

    Kremer, P; VanAndel, J


    The distribution patterns of life forms among extant families, subclasses and classes are described with the aim of detecting evolutionary trends. The explosive diversification of angiosperms constrains the possibilities for detecting such trends. Moreover, the extant groups of seed plants are only

  8. Exploring developmental, functional, and evolutionary aspects of amphioxus sensory cells

    Gouki Satoh


    Amphioxus has neither elaborated brains nor definitive sensory organs, so that the two may have evolved in a mutually affecting manner and given rise to the forms seen in extant vertebrates. Clarifying the developmental and functional aspects of the amphioxus sensory system is thus pivotal for inferring the early evolution of vertebrates. Morphological studies have identified and classified amphioxus sensory cells; however, it is completely unknown whether the morphological classification mak...

  9. Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study

    Rosa, João P. P.; de Souza, Altay A. L.; de Lima, Giscard H. O.; Rodrigues, Dayane F.; de Aquino Lemos, Valdir; da Silva Alves, Eduardo; Tufik, Sergio; de Mello, Marco T.


    Several studies have indicated that motivational level and prior expectations influence one’s commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (SDT, Self Determination Theory) and distal (evolutionary) explanations in the literature. This paper aims to verify if level of motivation (BREQ-2, Behavioral Regulation in Exercise Questionnaire-2) and expectations regarding regular physical exercise (IMPRAF-54) before starting a 1-year exercise...

  10. Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study.

    João Paulo Pereira Rosa


    Full Text Available Several studies have indicated that motivational level and prior expectations are relevant aspects to increase commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (Self Determination Theory and distal (evolutionary explanations in the literature. This paper aims to verify if level of motivation (BREQ-2 and expectations regarding regular physical exercise (IMPRAF-54 before starting a one-year exercise program could determine likelihood of completion. Ninety-four volunteers (53 women included a completed protocol group (CPG n=21 and drop-out group (DG n=73. The IMPRAF-54 scale was used to assess six different expectations associated with physical activity, and the BREQ-2 inventory was used to assess the level of motivation in five steps (from amotivation to intrinsic motivation. Both questionnaires were assessed before the regular exercise program. The CPG group presented higher sociability and lower pleasure scores according to IMPRAF-54 domains. A logistic regression showed that a one-point increment on sociability score increased the chance of completing the program by 10%, and the same one-point increment on pleasure score reduced the chance of completing the protocol by 16%. ROC curves were also calculated to establish IMPRAF-54 cutoffs for adherence (Sociability - 18.5 points – 81% sensibility/50% specificity and dropout (Pleasure – 25.5 points – 86% sensibility/20% specificity of the exercise protocol. Our results indicate that an expectation of social interaction was a positive factor in predicting adherence to exercise. Grounded in SDT and its innate needs (competence, autonomy, relatedness, physical exercise is not an end; it is a means to achieve autonomy and self-cohesion. The association of physical activity with social practices, like in hunter-gathering groups, can engage people to be physically active and can provide better results in adherence exercise programs for the

  11. Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study.

    Rosa, João P P; de Souza, Altay A L; de Lima, Giscard H O; Rodrigues, Dayane F; de Aquino Lemos, Valdir; da Silva Alves, Eduardo; Tufik, Sergio; de Mello, Marco T


    Several studies have indicated that motivational level and prior expectations influence one's commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (SDT, Self Determination Theory) and distal (evolutionary) explanations in the literature. This paper aims to verify if level of motivation (BREQ-2, Behavioral Regulation in Exercise Questionnaire-2) and expectations regarding regular physical exercise (IMPRAF-54) before starting a 1-year exercise program could determine likelihood of completion. Ninety-four volunteers (53 women) included a completed protocol group (CPG; n = 21) and drop-out group (n = 73). The IMPRAF-54 scale was used to assess six different expectations associated with physical activity, and the BREQ-2 inventory was used to assess the level of motivation in five steps (from amotivation to intrinsic motivation). Both questionnaires were assessed before starting a regular exercise program. The CPG group presented higher sociability and lower pleasure scores according to IMPRAF-54 domains. A logistic regression analysis showed that a one-point increment on sociability score increased the chance of completing the program by 10%, and the same one-point increment on pleasure score reduced the chance of completing the protocol by 16%. ROC curves were also calculated to establish IMPRAF-54 cutoffs for adherence (Sociability - 18.5 points - 81% sensibility/50% specificity) and dropout (Pleasure - 25.5 points - 86% sensibility/20% specificity) of the exercise protocol. Our results indicate that an expectation of social interaction was a positive factor in predicting adherence to exercise. Grounded in SDT and its innate needs (competence, autonomy, relatedness), physical exercise is not an end; it is a means to achieve autonomy and self-cohesion. The association of physical activity with social practices, as occurs in hunter-gathering groups, can engage people to be physically active and can provide better

  12. Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty

    Saenko Suzanne V


    Full Text Available Abstract Background The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. Results We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. Conclusions This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling. Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a

  13. Caspase Protocols in Mice

    Kaushal, Varsha; Herzog, Christian; Haun, Randy S.; Kaushal, Gur P.


    Members of the caspase family of proteases are evolutionarily conserved cysteine proteases that play a crucial role as the central executioners of the apoptotic pathway. Since the discovery of caspases, many methods have been developed to detect their activation and are widely used in basic and clinical studies. In a mouse tissue, caspase activation can be monitored by cleavage of caspase-specific synthetic substrates and by detecting cleaved caspase by western blot analysis of the tissue ext...

  14. Evolutionary dynamics on rugged fitness landscapes: exact dynamics and information theoretical aspects

    Saakian, David B


    The parallel mutation-selection evolutionary dynamics, in which mutation and replication are independent events, is solved exactly in the case that the Malthusian fitnesses associated to the genomes are described by the Random Energy Model (REM) and by a ferromagnetic version of the REM. The solution method uses the mapping of the evolutionary dynamics into a quantum Ising chain in a transverse field and the Suzuki-Trotter formalism to calculate the transition probabilities between configurations at different times. We find that in the case of the REM landscape the dynamics can exhibit three distinct regimes: pure diffusion or stasis for short times, depending on the fitness of the initial configuration, and a spin-glass regime for large times. The dynamic transition between these dynamical regimes is marked by discontinuities in the mean-fitness as well as in the overlap with the initial reference sequence. The relaxation to equilibrium is described by an inverse time decay. In the ferromagnetic REM, we find...

  15. Is perceived childlessness a cue for stereotyping? Evolutionary aspects of a social phenomenon.

    Kemkes, Ariane


    The present research investigates the moderating role of the "child factor" in impression formation. 307 university students (148 males, 159 females) were asked to assess 14 traits related to physical attractiveness, resource accruing potential, and emotional stability. The stimulus person was either accompanied by a child or shown individually. As expected, targets depicted with children were believed to be more family-committed and to possess greater parenting skills. The child factor also favourably biased respondents' assessments in terms of honesty, faithfulness, and maturity. Women with children were assumed to be less ambitious, while men with children were believed to be more generous and possess higher status and financial security. All results are discussed within the greater evolutionary context of kin selection and the "good-parent process". It is hypothesized that the negative stereotyping of the voluntary childfree is a by-product of cues that infer prosocial behaviour--similar to those used in mate selection. PMID:19350759

  16. Safety aspects of designs for future light water reactors (evolutionary reactors)

    The main purpose of this document is to describe the major innovations of proposed designs of future light water reactors, to describe specific safety characteristics and safety analysis methodologies, and to give a general overview of the most important safety aspects related to future reactors. The reactors considered in this report are limited to those intended for fixed station electrical power production, excluding most revolutionary concepts. More in depth discussion is devoted to those designs that are in a more advanced state of completion and have been more extensively described and analysed in the open literature. Other designs will be briefly described, as evidence of the large spectrum of new proposals. Some designs are similar; others implement unique features and require specific discussion (not all aspects of designs with unique features are fully discussed in this document). 131 refs, 22 figs

  17. Application of evolved evolutionary algorithms for the solution of different aspects of hydrothermal scheduling-a comprehensive overview

    Hydrothermal Scheduling (HTS) presents highly complicated, non-linear and multi-constrained optimization problem. Usually very turbulent and non-convex search space is linked with Hydrothermal (HT) Scheduling problem. So rather a robust and powerful optimization tool is required to optimize this problem efficiently. In literature, so far, many powerful and robust optimization algorithms have been employed for the solution of HTS problem. Genetic Algorithm (GA) represents one of the most established while Bacterial Foraging Algorithm (BFA) represents one of the newest Evolutionary Algorithms. Both GA and BFA are being actively deployed to solve non convex optimization problems, where conventional approaches have rather failed to provide acceptable results. The aim of this research paper is to provide a comprehensive survey of literature related to both GA and BFA as effective optimization algorithms for the solution of various aspects of HTS problem. The outcomes alongwith both strengths and weaknesses of individual algorithms are also discussed. (author)

  18. Caspases: An apoptosis mediator

    Tapan Kumar Palai


    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  19. Evolutionary aspects of non-cell-autonomous regulation in vascular plants: structural background and models to study

    Anastasiia I. Evkaikina; Marina A. Romanova; Olga V. Voitsekhovskaja


    Plasmodesmata (PD) serve for the exchange of information in form of miRNA, proteins, and mRNA between adjacent cells in the course of plant development. This fundamental role of PD is well established in angiosperms but has not yet been traced back to the evolutionary ancient plant taxa where functional studies lag behind studies of PD structure and ontogenetic origin. There is convincing evidence that the ability to form secondary (post-cytokinesis) PD, which can connect any adjacent cells, ...

  20. Allosteric modulation of caspases.

    Häcker, Hans-Georg; Sisay, Mihiret Tekeste; Gütschow, Michael


    Caspases are proteolytic enzymes mainly involved in the induction and execution phases of apoptosis. This type of programmed cell death is an essential regulatory process required to maintain the integrity and homeostasis of multicellular organisms. Inappropriate apoptosis is attributed a key role in many human diseases, including neurodegenerative disorders, ischemic damage, autoimmune diseases and cancer. Allosteric modulation of the function of a protein occurs when the regulatory trigger, such as the binding of a small effector or inhibitor molecule, takes place some distance from the protein's active site. In recent years, several caspases have been identified that possess allosteric sites and binding of small molecule to these sites resulted in the modulation of enzyme activities. Regulation of caspase activity by small molecule allosteric modulators is believed to be of great therapeutic importance. In this review we give brief highlights on recent developments in identifying and characterizing natural and synthetic allosteric inhibitors as well as activators of caspases and discuss their potential in drug discovery and protein engineering. PMID:21807025

  1. Caspase Family Proteases and Apoptosis

    Ting-Jun FAN; Li-Hui HAN; Ri-Shan CONG; Jin LIANG


    Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated in an orderly way by a series of signal cascades under certain circumstances. The caspase-cascade system plays vital roles in the induction, transduction and amplification of intracellular apoptotic signals. Caspases, closely associated with apoptosis, are aspartate-specific cysteine proteases and members of the interleukin-1β-converting enzyme family. The activation and function of caspases, involved in the delicate caspase-cascade system, are regulated by various kinds of molecules, such as the inhibitor of apoptosis protein, Bcl-2 family proteins, calpain,and Ca2+. Based on the latest research, the members of the caspase family, caspase-cascade system and caspase-regulating molecules involved in apoptosis are reviewed.

  2. Evolutionary history of the PER3 variable number of tandem repeats (VNTR: idiosyncratic aspect of primate molecular circadian clock.

    Flávia Cal Sabino

    Full Text Available The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  3. Evolutionary Computation:ao Overview

    HeZhenya; WeiChengjian


    Evolutionary computation is a field of simulating evolution on a computer.Both aspects of it ,the problem solving aspect and the aspect of modeling natural evolution,are important.Simulating evolution on a computer results in stochastic optimization techniques that can outperform classical methods of optimization when applied to difficult real-world problems.There are currently four main avenues of research in simulated evolution:genetic algorithms,evolutionary programming,evolution strategies,and genetic programming.This paper presents a brief overview of thd field on evolutionary computation,including some theoretical issues,adaptive mechanisms,improvements,constrained optimizqtion,constrained satisfaction,evolutionary neural networks,evolutionary fuzzy systems,hardware evolution,evolutionary robotics,parallel evolutionary computation,and co-evolutionary models.The applications of evolutionary computation for optimizing system and intelligent information processing in telecommunications are also introduced.

  4. Structural, functional, and evolutionary aspects of galectins in aquatic mollusks: From a sweet tooth to the Trojan horse.

    Vasta, G R; Feng, C; Bianchet, M A; Bachvaroff, T R; Tasumi, S


    Galectins constitute a conserved and widely distributed lectin family characterized by their binding affinity for β-galactosides and a unique binding site sequence motif in the carbohydrate recognition domain (CRD). In spite of their structural conservation, galectins display a remarkable functional diversity, by participating in developmental processes, cell adhesion and motility, regulation of immune homeostasis, and recognition of glycans on the surface of viruses, bacteria and protozoan parasites. In contrast with mammals, and other vertebrate and invertebrate taxa, the identification and characterization of bona fide galectins in aquatic mollusks has been relatively recent. Most of the studies have focused on the identification and domain organization of galectin-like transcripts or proteins in diverse tissues and cell types, including hemocytes, and their expression upon environmental or infectious challenge. Lectins from the eastern oyster Crassostrea virginica, however, have been characterized in their molecular, structural and functional aspects and some notable features have become apparent in the galectin repertoire of aquatic mollusks. These including less diversified galectin repertoires and different domain organizations relative to those observed in vertebrates, carbohydrate specificity for blood group oligosaccharides, and up regulation of galectin expression by infectious challenge, a feature that supports their proposed role(s) in innate immune responses. Although galectins from some aquatic mollusks have been shown to recognize microbial pathogens and parasites and promote their phagocytosis, they can also selectively bind to phytoplankton components, suggesting that they also participate in uptake and intracellular digestion of microalgae. In addition, the experimental evidence suggests that the protozoan parasite Perkinsus marinus has co-evolved with the oyster host to be selectively recognized by the oyster hemocyte galectins over algal food

  5. Roles of inflammatory caspases during processing of zebrafish interleukin-1β in Francisella noatunensis infection

    Vojtech, Lucia N.; Scharping, Nichole; Woodson, James C.; Hansen, John D.


    The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.                   

  6. Music and evolutionary computation

    Reis, Cecília; Marques, Viriato M.; Machado, J. A. Tenreiro


    This paper presents a brief history of the western music: from its genesis to serialism and the Darmstadt school. Also some mathematical aspects of music are then presented and confronted with music as a form of art. The question is, are these two distinct aspects compatible? Can computers be of real help in automatic composition? The more appealing algorithmic approach is evolutionary computation as it offers creativity potential. Therefore, the Evolutionary Algorithms are then introduced an...

  7. Polymorphic Evolutionary Games.

    Fishman, Michael A


    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game. PMID:27016340

  8. Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis.

    Milhas, Delphine; Cuvillier, Olivier; Therville, Nicole; Clavé, Patricia; Thomsen, Mogens; Levade, Thierry; Benoist, Hervé; Ségui, Bruno


    In contrast to caspase-8, controversy exists as to the ability of caspase-10 to mediate apoptosis in response to FasL. Herein, we have shown activation of caspase-10, -3, and -7 as well as B cell lymphoma-2-interacting domain (Bid) cleavage and cytochrome c release in caspase-8-deficient Jurkat (I9-2) cells treated with FasL. Apoptosis was clearly induced as illustrated by nuclear and DNA fragmentation. These events were inhibited by benzyloxycarbonyl-VAD-fluoromethyl ketone, a broad spectrum caspase inhibitor, indicating that caspases were functionally and actively involved. Benzyloxycarbonyl-AEVD-fluoromethyl ketone, a caspase-10 inhibitor, had a comparable effect. FasL-induced cell death was not completely abolished by caspase inhibitors in agreement with the existence of a cytotoxic caspase-independent pathway. In subpopulations of I9-2 cells displaying distinct caspase-10 expression levels, cell sensitivity to FasL correlated with caspase-10 expression. A robust caspase activation, Bid cleavage, and DNA fragmentation were observed in cells with high caspase-10 levels but not in those with low levels. In vitro, caspase-10, as well as caspase-8, could cleave Bid to generate active truncated Bid (p15). Altogether, our data strongly suggest that caspase-10 can serve as an initiator caspase in Fas signaling leading to Bid processing, caspase cascade activation, and apoptosis. PMID:15772077

  9. Caspase exploitation by Legionella pneumophila

    Kathrin eKrause; Amer, Amal O.


    Legionella pneumophila remains a major health concern, especially for hospitalized patients. L. pneumophila in the environment can survive extracellular or as protozoan parasite within amoeba. After human infection it efficiently replicates in alveolar macrophages without activating inflammasome assembly and cleavage of caspase-1. In contrast murine macrophages actively recognize intracellular L. pneumophila via inflammasome components which initiate pro-inflammatory cytokine secretion, phago...

  10. Caspase Exploitation by Legionella pneumophila

    Krause, Kathrin; Amer, Amal O.


    Legionella pneumophila remains a major health concern, especially for hospitalized patients. L. pneumophila in the environment can survive extracellular or as protozoan parasite within amoeba. After human infection it efficiently replicates in alveolar macrophages without activating inflammasome assembly and cleavage of caspase-1. In contrast murine macrophages actively recognize intracellular L. pneumophila via inflammasome components which initiate pro-inflammatory cytokine secretion, phago...

  11. Structural Features of Caspase-Activating Complexes

    Hyun Ho Park


    Full Text Available Apoptosis, also called programmed cell death, is an orderly cellular suicide program that is critical for the development, immune regulation and homeostasis of a multi-cellular organism. Failure to control this process can lead to serious human diseases, including many types of cancer, neurodegenerative diseases, and autoimmununity. The process of apoptosis is mediated by the sequential activation of caspases, which are cysteine proteases. Initiator caspases, such as caspase-2, -8, -9, and -10, are activated by formation of caspase-activating complexes, which function as a platform to recruit caspases, providing proximity for self-activation. Well-known initiator caspase-activating complexes include (1 DISC (Death Inducing Signaling Complex, which activates caspases-8 and 10; (2 Apoptosome, which activates caspase-9; and (3 PIDDosome, which activates caspase-2. Because of the fundamental biological importance of capases, many structural and biochemical studies to understand the molecular basis of assembly mechanism of caspase-activating complexes have been performed. In this review, we summarize previous studies that have examined the structural and biochemical features of caspase-activating complexes. By analyzing the structural basis for the assembly mechanism of the caspase-activating complex, we hope to provide a comprehensive understanding of caspase activation by these important oligomeric complexes.

  12. Revisiting Caspase-11 Function in Host Defense

    Ng, Tessie M.; Monack, Denise M.


    Pro-inflammatory caspases play important roles in innate immunity. Much attention has focused on caspase-1, which acts to eliminate pathogens by obliterating their replicative niches as well as alerting the host to their presence. Emerging data now sheds light on the lesser-studied pro-inflammatory caspase-11 in the combat between host and pathogen. With new tools available, researchers are now further elucidating the mechanisms by which caspase-11 contributes to host defense. Here, we review...

  13. Small-molecule caspase inhibitors

    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  14. Small-molecule caspase inhibitors

    Zhenodarova, S M [Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation)


    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  15. Small-molecule caspase inhibitors

    Zhenodarova, S. M.


    The review considers low-molecular weight inhibitors of caspases, cysteine proteases being key contributors to apoptosis (programmed cell death). The inhibitors with aspartic acid residues or various heterocyclic systems (both synthetic and natural) are covered. Their possible mechanisms of action are discussed. Data on inhibitor structure-activity relationship studies are systematically surveyed. The interactions of the non-peptide fragments of an inhibitor with the enzymes are examined. Examples of the use of some inhibitors for apoptosis suppression are provided.

  16. Phylogenomics of caspase-activated DNA fragmentation factor

    The degradation of nuclear DNA by DNA fragmentation factor (DFF) is a key step in apoptosis of mammalian cells. Using comparative genomics, we have here determined the evolutionary history of the genes encoding the two DFF subunits, DFFA (also known as ICAD) and DFFB (CAD). Orthologs of DFFA and DFFB were identified in Nematostella vectensis, a representative of the primitive metazoan clade cnidarians, and in various vertebrates and insects, but not in representatives of urochordates, echinoderms, and nematodes. The domains mediating the interaction of DFFA and DFFB, a caspase cleavage site in DFFA, and the amino acid residues critical for endonuclease activity of DFFB were conserved in Nematostella. These findings suggest that DFF has been a part of the primordial apoptosis system of the eumetazoan common ancestor and that the ancient cell death machinery has degenerated in several evolutionary lineages, including the one leading to the prototypical apoptosis model, Caenorhabditis elegans

  17. Evolutionary Expectations

    Nash, Ulrik William


    The concept of evolutionary expectations descends from cue learning psychology, synthesizing ideas on rational expectations with ideas on bounded rationality, to provide support for these ideas simultaneously. Evolutionary expectations are rational, but within cognitive bounds. Moreover, they are...... cognitive bounds will perceive business opportunities identically. In addition, because cues provide information about latent causal structures of the environment, changes in causality must be accompanied by changes in cognitive representations if adaptation is to be maintained. The concept of evolutionary...

  18. Evolutionary Computing

    Eiben, Aguston; Schoenauer, Marc


    Evolutionary computing (EC) is an exciting development in Computer Science. It amounts to building, applying and studying algorithms based on the Darwinian principles of natural selection. In this paper we briefly introduce the main concepts behind evolutionary computing. We present the main components all evolutionary algorithms (EA), sketch the differences between different types of EAs and survey application areas ranging from optimization, modeling and simulation to entertainment.

  19. Caspase-7 and dental apoptosis

    Matalová, Eva; Tucker, A. S.; Švandová, Eva; Berghe, T.V.; Sharpe, P. T.

    Fyziologický ústav AV ČR, v. v. i.. Roč. 60, č. 4 (2011), 35P-35P ISSN 0862-8408. [Proceedings of the Czech and Slovak Physiological Societies. 09.02.2011-11.02.2011, Bratislava] R&D Projects: GA AV ČR KJB500450802; GA AV ČR IAA600450904 Institutional research plan: CEZ:AV0Z50450515 Keywords : caspase * protein * dental Subject RIV: ED - Physiology

  20. Molecular cloning, immunohistochemical localization, characterization and expression analysis of caspase-9 from the purse red common carp (Cyprinus carpio) exposed to cadmium

    Gao, Dian; Xu, Zhen’e [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Zhang, Xiaoyan [Medical College of Nanchang University, Nanchang 330006 (China); Wang, Hongmei [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Wang, Yannan [Medical College of Nanchang University, Nanchang 330006 (China); Min, Weiping, E-mail: [Medical College of Nanchang University, Nanchang 330006 (China); Institute of Immunotherapy, Nanchang University, Nanchang 330006 (China); Jiangxi Academy of Medical Sciences, Nanchang 330006 (China)


    Highlights: •The cDNA of caspase-9 in common carp was cloned. •The evolutionary conservation including caspase recruitment domain, large and small subunits was clarified. •The mRNA level of caspase-9 cannot be used as a major marker at an earlier point in the apoptotic cascade. •Caspase-9 cleavage form was detected. •Immunopositive staining was limited to the cytoplasm of renal tubular epithelial cells. -- Abstract: Caspase-9, the essential initiator caspase is believed to play a central role in mitochondria-mediated apoptosis signaling. In this study, we isolated the caspase-9 gene from common carp, one of the most important industrial aquatic animals in China using rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of caspase-9, composed of 436 amino acids, showed approximately 47.6% identity and 64.7% similarity to human caspase-9. It also possessed a conserved caspase-associated recruitment domain (CARD), a large subunit and a small subunit. Phylogenetic analysis clearly demonstrated that caspase-9 formed a clade with cyprinid fish caspase-9. Real-time quantitative PCR analysis revealed that caspase-9 transcripts were not significantly increased in kidney after exposure to cadmium (Cd). Whereas caspase-9 cleaved fragments were detected using Western blot analysis with the same Cd treatment condition. Furthermore, the result of immunohistochemical detection showed immunoreactivities were predominantly limited to the cytoplasm of renal tubular epithelial cells and no remarkable changes of immunopositive staining were observed after Cd treatment. Accordingly, the results signify that caspase-9 may play an essential role in Cd induced apoptosis.

  1. Molecular cloning, immunohistochemical localization, characterization and expression analysis of caspase-9 from the purse red common carp (Cyprinus carpio) exposed to cadmium

    Highlights: •The cDNA of caspase-9 in common carp was cloned. •The evolutionary conservation including caspase recruitment domain, large and small subunits was clarified. •The mRNA level of caspase-9 cannot be used as a major marker at an earlier point in the apoptotic cascade. •Caspase-9 cleavage form was detected. •Immunopositive staining was limited to the cytoplasm of renal tubular epithelial cells. -- Abstract: Caspase-9, the essential initiator caspase is believed to play a central role in mitochondria-mediated apoptosis signaling. In this study, we isolated the caspase-9 gene from common carp, one of the most important industrial aquatic animals in China using rapid amplification of cDNA ends (RACE). The deduced amino acid sequence of caspase-9, composed of 436 amino acids, showed approximately 47.6% identity and 64.7% similarity to human caspase-9. It also possessed a conserved caspase-associated recruitment domain (CARD), a large subunit and a small subunit. Phylogenetic analysis clearly demonstrated that caspase-9 formed a clade with cyprinid fish caspase-9. Real-time quantitative PCR analysis revealed that caspase-9 transcripts were not significantly increased in kidney after exposure to cadmium (Cd). Whereas caspase-9 cleaved fragments were detected using Western blot analysis with the same Cd treatment condition. Furthermore, the result of immunohistochemical detection showed immunoreactivities were predominantly limited to the cytoplasm of renal tubular epithelial cells and no remarkable changes of immunopositive staining were observed after Cd treatment. Accordingly, the results signify that caspase-9 may play an essential role in Cd induced apoptosis

  2. Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12.

    García de la Cadena, Selene; Massieu, Lourdes


    Caspases are cysteine proteases, which play important roles in different processes including, apoptosis and inflammation. Caspase-12, expressed in mouse and human, is classified as an inflammatory caspase. However, in humans caspase-12 gene has acquired different mutations that result in the expression of different variants. Caspase-12 is generally recognized as a negative regulator of the inflammatory response induced by infections, because it inhibits the activation of caspase-1 in inflammasome complexes, the production of the pro-inflammatory cytokines IL-1β and IL-18 and the overall response to sepsis. In contrast, caspase-4, the human paralog of caspase-12, exerts a positive modulatory action of the inflammatory response to infectious agents. The role of caspase-12 and caspase-4 in inflammation associated with cerebral ischemia, a condition that results from a transient or permanent reduction of cerebral blood flow, is still unknown. Among the mechanisms involved in ischemic brain injury, apoptosis and inflammation have important roles. Under these conditions, disturbances in the homeostasis of the endoplasmic reticulum (ER) take place, leading to ER stress, caspase activation and apoptosis. Caspase-12 up-regulation and processing has been observed after the ischemic episode but its role in apoptosis is controversial. Cleavage of caspase-4 also occurs during ER stress but its role in ischemic brain injury is unknown. Throughout this review evidence supporting a role of caspase-12 and caspase-4 on the modulation of the inflammatory response to infection and their potential contribution to ER stress-induced apoptosis, is discussed. Understanding the actions of rodent caspase-12 and human caspase-4 will help us to elucidate their role in different pathological conditions, which to date is not well understood. PMID:27142195

  3. Caspase Exploitation by Legionella pneumophila

    Krause, Kathrin; Amer, Amal O.


    Legionella pneumophila remains a major health concern, especially for hospitalized patients. L. pneumophila in the environment can survive extracellular or as protozoan parasite within amoeba. After human infection it efficiently replicates in alveolar macrophages without activating inflammasome assembly and cleavage of caspase-1. In contrast murine macrophages actively recognize intracellular L. pneumophila via inflammasome components which initiate pro-inflammatory cytokine secretion, phagosomal maturation and pyroptotic cell death thereby leading to bacterial restriction. During this process flagellin-dependent and -independent signaling pathways trigger the canonical as well as the non-canonical inflammasome. This review describes the current knowledge about L. pneumophila-induced inflammasome pathways in permissive and restrictive host cells. PMID:27148204

  4. Evolutionary Economics

    Dopfer, Kurt


    The paper provides an overview of major recent contributions in evolutionary economics. It starts of demonstrating that the pioneers of this approach such as Veblen, Schumpeter, Marshall and Hayek saw the economy as continuously changing and that this kind of "realism of perception" guides essentially also contemporary evolutionary economics. The economy is viewed as an evolving system of structured knowledge governing economic operations. Theoretically, a micro-meso-macro architecture is pro...

  5. Evolutionary algorithms

    Szöllösi, Tomáš


    The first part of this work deals with the optimization and evolutionary algorithms which are used as a tool to solve complex optimization problems. The discussed algorithms are Differential Evolution, Genetic Algorithm, Simulated Annealing and deterministic non-evolutionary algorithm Taboo Search.. Consequently the discussion is held on the issue of testing the optimization algorithms through the use of the test function gallery and comparison solution all algorithms on Travelling salesman p...

  6. Evolutionary algorithms

    Eremeev, Anton V.


    This manuscript contains an outline of lectures course "Evolutionary Algorithms" read by the author in Omsk State University n.a. F.M.Dostoevsky. The course covers Canonic Genetic Algorithm and various other genetic algorithms as well as evolutioanry algorithms in general. Some facts, such as the Rotation Property of crossover, the Schemata Theorem, GA performance as a local search and "almost surely" convergence of evolutionary algorithms are given with complete proofs. The text is in Russian.

  7. Pharmacological caspase inhibitors: Research towards therapeutic perspectives

    Kudělová, J.; Fleischmannová, Jana; Adamová, Eva; Matalová, Eva


    Roč. 66, č. 4 (2015), s. 473-482. ISSN 0867-5910 R&D Projects: GA ČR GB14-37368G Institutional support: RVO:67985904 Keywords : caspase * caspase inhibitor * apoptosis Subject RIV: EA - Cell Biology Impact factor: 2.386, year: 2014

  8. Evolutionary awareness.

    Gorelik, Gregory; Shackelford, Todd K


    In this article, we advance the concept of "evolutionary awareness," a metacognitive framework that examines human thought and emotion from a naturalistic, evolutionary perspective. We begin by discussing the evolution and current functioning of the moral foundations on which our framework rests. Next, we discuss the possible applications of such an evolutionarily-informed ethical framework to several domains of human behavior, namely: sexual maturation, mate attraction, intrasexual competition, culture, and the separation between various academic disciplines. Finally, we discuss ways in which an evolutionary awareness can inform our cross-generational activities-which we refer to as "intergenerational extended phenotypes"-by helping us to construct a better future for ourselves, for other sentient beings, and for our environment. PMID:25300054

  9. Evolutionary macroecology

    José Alexandre F. Diniz-Filho


    Full Text Available Macroecology focuses on ecological questions at broad spatial and temporal scales, providing a statistical description of patterns in species abundance, distribution and diversity. More recently, historical components of these patterns have begun to be investigated more deeply. We tentatively refer to the practice of explicitly taking species history into account, both analytically and conceptually, as ‘evolutionary macroecology’. We discuss how the evolutionary dimension can be incorporated into macroecology through two orthogonal and complementary data types: fossils and phylogenies. Research traditions dealing with these data have developed more‐or‐less independently over the last 20–30 years, but merging them will help elucidate the historical components of diversity gradients and the evolutionary dynamics of species’ traits. Here we highlight conceptual and methodological advances in merging these two research traditions and review the viewpoints and toolboxes that can, in combination, help address patterns and unveil processes at temporal and spatial macro‐scales.

  10. Evolutionary computation for trading systems

    Kaucic, Massimiliano


    Evolutionary computations, also called evolutionary algorithms, consist of several heuristics, which are able to solve optimization tasks by imitating some aspects of natural evolution. They may use different levels of abstraction, but they are always working on populations of possible solutions for a given task. The basic idea is that if only those individuals of a population which meet a certain selection criteria reproduce, while the remaining individuals die, the population wi...

  11. A designed redox-controlled caspase

    Witkowski, Witold A.; Hardy, Jeanne A. (UMASS, Amherst)


    Caspases are a powerful class of cysteine proteases. Introduction of activated caspases in healthy or cancerous cells results in induction of apoptotic cell death. In this study, we have designed and characterized a version of caspase-7 that can be inactivated under oxidizing extracellular conditions and then reactivated under reducing intracellular conditions. This version of caspase-7 is allosterically inactivated when two of the substrate-binding loops are locked together via an engineered disulfide. When this disulfide is reduced, the protein regains its full function. The inactive loop-locked version of caspase-7 can be readily observed by immunoblotting and mass spectrometry. The reduced and reactivated form of the enzyme observed crystallographically is the first caspase-7 structure in which the substrate-binding groove is properly ordered even in the absence of an active-site ligand. In the reactivated structure, the catalytic-dyad cysteine-histidine are positioned 3.5 {angstrom} apart in an orientation that is capable of supporting catalysis. This redox-controlled version of caspase-7 is particularly well suited for targeted cell death in concert with redox-triggered delivery vehicles.

  12. Inactivation of Effector Caspases through Nondegradative Polyubiquitylation

    Ditzel, Mark; Broemer, Meike; Tenev, Tencho;


    Ubiquitin-mediated inactivation of caspases has long been postulated to contribute to the regulation of apoptosis. However, detailed mechanisms and functional consequences of caspase ubiquitylation have not been demonstrated. Here we show that the Drosophila Inhibitor of Apoptosis 1, DIAP1, blocks...... reduces the caspase's proteolytic velocity. Disruption of drICE ubiquitylation, either by mutation of DIAP1's E3 activity or drICE's ubiquitin-acceptor lysines, abrogates DIAP1's ability to neutralize drICE and suppress apoptosis in vivo. We also show that DIAP1 rests in an "inactive" conformation that...

  13. Function of caspase-14 in trophoblast differentiation

    Charles Adrian K


    Full Text Available Abstract Background Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

  14. Evolutionary Psychology

    Heylighen, Francis


    Evolutionary psychology (EP) is an approach to the study of the mind that is founded on Darwin’s theory of evolution by natural selection. It assumes that our mental abilities, emotions and preferences are adapted specifically for solving problems of survival and reproduction in humanity’s ancestral environment, and derives testable predictions from this assumption. This has important implications for our understanding of the conditions for human well-being.

  15. Ripoptosome Analysis by Caspase-8 Coimmunoprecipitation.

    Feoktistova, Maria; Geserick, Peter; Leverkus, Martin


    The biochemical signaling of cell death pathways is executed at a number of different intracellular and/or membrane-bound high-molecular mass complexes. It is crucial to be able to detect the formation, differences in assembly, and differential composition of such complexes to understand their contribution to the execution phase of apoptotic or necroptotic cell death. We describe here the use of caspase-8 coimmunoprecipitation in the spontaneously transformed keratinocyte cell line, HaCaT, to study the formation and composition of the Ripoptosome, a complex that is based on the serine-threonine kinase receptor-interacting protein 1 (RIPK1). However, the method can be adapted for use with other antibodies and cell lines. This protocol determines whether cells form the Ripoptosome complex, which is important for both apoptosis and necroptosis execution. Caspase-8 is an indispensible Ripoptosome component; therefore, caspase-8 antibodies are used to pull down the respective complex. However, the method cannot discriminate whether this complex triggers apoptosis (through the RIPK1 → FADD → caspase-8 activation pathway), necroptosis (through the RIPK1 → RIPK3 → MLKL activation pathway) or nondeath signaling. The actual signaling output (death or nondeath signaling) depends on the stoichiometry of the respective molecules as well as on the activity of FLIP, caspase-8, or other factors. PMID:26933246

  16. Evolutionary thinking

    Hunt, Tam


    Evolution as an idea has a lengthy history, even though the idea of evolution is generally associated with Darwin today. Rebecca Stott provides an engaging and thoughtful overview of this history of evolutionary thinking in her 2013 book, Darwin's Ghosts: The Secret History of Evolution. Since Darwin, the debate over evolution—both how it takes place and, in a long war of words with religiously-oriented thinkers, whether it takes place—has been sustained and heated. A growing share of this de...

  17. Consciousness and the brain: evolutionary aspects.

    Towers, B


    Self-reflective consciousness is distinguished from 'simple' awareness and from conscious awareness. Awareness is a fundamental property of living matter as it reacts to environmental stimuli. A hypothesis is advanced to account for the general phenomenon of decussation of nerve fibres in the central nervous system of vertebrates. This feature, the crossing over of nerve fibres to the opposite side of the brain, is interpreted as exemplifying the inherent caution of living forms. The evolution of increasing complexity of structure in spinal cord and brain is a prerequisite for increasing awareness of the environment and for increasing freedom from its constraints. Conscious awareness is manifested in living forms primarily when they are learning to respond either to new stimuli or to internal demands such as breathing and walking. The relegation of learnt activities to the realm of unconscious reflex allows for concentration on new and more complex responses, which leads to further freedom of action. The seeming simplicity of human thinking rests on the increasing complexity of the evolving brain and of appropriate responses learnt during phylogenetic development. The human brain and its thinking functions are basically trustworthy because they are rooted in biological evolution. PMID:261656

  18. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  19. Coxsackievirus B3-induced apoptosis and Caspase-3



    Cell death can be classified into two categories: apoptosis and necrosis. Apoptotic pathway can beeither caspase-dependent or caspase-independent. Caspase-independent cytopathic effect (CPE) has beendescribed. In order to evaluate the pattern of HeLa cell death induced by Coxsackievirus B3 (CVB3)and whether apoptosis involves caspase activation, we co-cultivated HeLa cells with CVB3 and detectedthe cytopathic changes, the alteration of mRNA and protein expression of caspase-3 gene plus caspase-3activity, as well as analyzing DNA fragmentation before and after caspase-3 activity inhibition. Accordingto the results, we propose that CVB3 may induce apoptosis and necrosis in HeLa cells, the latter appearingmuch earlier. Caspase-3 is activated at the levels of both transcription and translation, and procaspase-3 isproteolytically cleaved, thus leading to the continuous increasing of both caspase-3 precursor protein and itssubunit. However, besides CPE, apoptosis induced by CVB3 is not a direct consequence of the activationof caspase-3, or caspase-3 is not the only effector molecule in apoptotic cell death, for caspase-3 inhibitorcan not decrease DNA fragmentation. Some other biochemical mechanisms may participate in the process,whose role weakens the effect of inhibiting caspase-3 activity.

  20. Evolutionary Information Theory

    Mark Burgin


    Evolutionary information theory is a constructive approach that studies information in the context of evolutionary processes, which are ubiquitous in nature and society. In this paper, we develop foundations of evolutionary information theory, building several measures of evolutionary information and obtaining their properties. These measures are based on mathematical models of evolutionary computations, machines and automata. To measure evolutionary information in an invariant form, we const...

  1. Proteasomal regulation of caspase-8 in cancer cell apoptosis

    Fiandalo, Michael V.; Schwarze, Steven R.; Kyprianou, Natasha


    Previous studies demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of caspase-8. The present study investigated the impact of proteasome inhibition on caspase-8 stability, ubiquitination, trafficking, and activation in cancer cells. Using caspase-8 deficient neuroblastoma (NB7) cells for reconstituting non-cleavable mutant forms of caspase-8, we demonstrated that the non-cleavable fo...

  2. Interactive Evolutionary Algorithms for Image Enhancement and Creation

    Mist, Joseph James


    Image enhancement and creation, particularly for aesthetic purposes, are tasks for which the use of interactive evolutionary algorithms would seem to be well suited. Previous work has concentrated on the development of various aspects of the interactive evolutionary algorithms and their application to various image enhancement and creation problems. Robust evaluation of algorithmic design options in interactive evolutionary algorithms and the comparison of interactive evolutionary algorithms ...

  3. Allopurinol’s effect on caspase-3 and caspase-8 activity in hypoxic-ischemic newborn rats

    Kenan Özcan; Mehmet Satar; Necmiye Canacankatan; Erdal Taşkın; Kenan Dağlıoğlu


    Aim: During reperfusion period of hypoxia-ischemia, cyclooxygenase and xanthine oxidase pathways are induced. A xanthine oxidase inhibitor, allopurinol has been shown to be neuroprotective in hypoxic- ischemic encephalopathy. Caspase-8 and caspase-3 have a key role in neuronal apoptosis. We aimed to test repeated doses of allopurinol’s effect on caspase-3 and caspase-8 activities in newborn rats with hypoxic-ischemic encephalopathy. Material and Method: Seven days old newborn rats were taken ...

  4. Delayed activation of caspase-independent apoptosis during heart failure in transgenic mice overexpressing caspase inhibitor CrmA

    Bae, Soochan; Siu, Parco M.; Choudhury, Sangita; Ke, Qingen; Choi, Jun H.; Koh, Young Y.; Kang, Peter M.


    Although caspase activation is generally thought to be necessary to induce apoptosis, recent evidence suggests that apoptosis can be activated in the setting of caspase inhibition. In this study, we tested the hypothesis that caspase-independent apoptotic pathways contribute to the development of heart failure in the absence of caspase activation. Acute cardiomyopathy was induced using a single dose of doxorubicin (Dox, 20 mg/kg) injected into male wild-type (WT) and transgenic (Tg) mice with...

  5. Allosteric modulation of caspase 3 through mutagenesis

    Jad Walters


    Full Text Available A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to His266 at two sites in the interface, E124A and Y197C. We present results from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double and triple mutants. The results demonstrate that considering allosteric inhibition of caspase 3 as a shift between discrete ‘off-state’ or ‘on-state’ conformations is insufficient. Although His266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase 3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble.

  6. The Enigmatic Roles of Caspases in Tumor Development

    One function ascribed to apoptosis is the suicidal destruction of potentially harmful cells, such as cancerous cells. Hence, their growth depends on evasion of apoptosis, which is considered as one of the hallmarks of cancer. Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. From clinical data, however, there is little evidence that caspase genes are impaired in cancer. Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. There is experimental evidence from transgenic mice that certain initiator caspases, such as caspase-8 and -2, might act as tumor suppressors. Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. These data seem to question a general tumor-suppressive role of caspases. We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. Third, pathways upstream of caspase activation might be disrupted in tumor cells. Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. These scenarios, however, are hardly compatible with the considerable frequency of spontaneous apoptosis occurring in several cancer types. Therefore, alternative concepts might come into play, such as compensatory proliferation. Herein, apoptosis and/or non-apoptotic functions of caspases may

  7. Evolutionary Information Theory

    Mark Burgin


    Full Text Available Evolutionary information theory is a constructive approach that studies information in the context of evolutionary processes, which are ubiquitous in nature and society. In this paper, we develop foundations of evolutionary information theory, building several measures of evolutionary information and obtaining their properties. These measures are based on mathematical models of evolutionary computations, machines and automata. To measure evolutionary information in an invariant form, we construct and study universal evolutionary machines and automata, which form the base for evolutionary information theory. The first class of measures introduced and studied in this paper is evolutionary information size of symbolic objects relative to classes of automata or machines. In particular, it is proved that there is an invariant and optimal evolutionary information size relative to different classes of evolutionary machines. As a rule, different classes of algorithms or automata determine different information size for the same object. The more powerful classes of algorithms or automata decrease the information size of an object in comparison with the information size of an object relative to weaker4 classes of algorithms or machines. The second class of measures for evolutionary information in symbolic objects is studied by introduction of the quantity of evolutionary information about symbolic objects relative to a class of automata or machines. To give an example of applications, we briefly describe a possibility of modeling physical evolution with evolutionary machines to demonstrate applicability of evolutionary information theory to all material processes. At the end of the paper, directions for future research are suggested.

  8. Does Caspase-6 Have a Role in Perinatal Brain Injury?

    Baburamani, Ana A.; Miyakuni, Yasuka; Vontell, Regina; Supramaniam, Veena G.; Svedin, Pernilla; Rutherford, Mary; Gressens, Pierre; Mallard, Carina; Takeda, Satoru; Thornton, Claire; Hagberg, Henrik


    Apoptotic mechanisms are centre stage for the development of injury in the immature brain, and caspases have been shown to play a pivotal role during brain development and in response to injury. The inhibition of caspases using broad-spectrum agents such as Q-VD-OPh is neuroprotective in the immature brain. Caspase-6, an effector caspase, has been widely researched in neurodevelopmental disorders and found to be important following adult stroke, but its function in the neonatal brain has yet to be detailed. Furthermore, caspases may be important in microglial activation; microglia are required for optimal brain development and following injury, and their close involvement during neuronal cell death suggests that apoptotic cues such as caspase activation may be important in microglial activation. Therefore, in this study we aimed to investigate the possible apoptotic and non-apoptotic functions caspase-6 may have in the immature brain in response to hypoxia-ischaemia. We examined whether caspases are involved in microglial activation. We assessed cleaved caspase-6 expression following hypoxia-ischaemia and conducted primary microglial cultures to assess whether the broad-spectrum inhibitor Q-VD-OPh or caspase-6 gene deletion affected lipopolysaccharide (LPS)-mediated microglial activation and phenotype. We observed cleaved caspase-6 expression to be low but present in the cell body and cell processes in both a human case of white matter injury and 72 h following hypoxia-ischaemia in the rat. Gene deletion of caspase-6 did not affect the outcome of brain injury following mild (50 min) or severe (60 min) hypoxia-ischaemia. Interestingly, we did note that cleaved caspase-6 was co-localised with microglia that were not of apoptotic morphology. We observed that mRNA of a number of caspases was modulated by low-dose LPS stimulation of primary microglia. Q-VD-OPh treatment and caspase-6 gene deletion did not affect microglial activation but modified slightly the M2b

  9. Comparative genomics reveals conservation of filaggrin and loss of caspase-14 in dolphins.

    Strasser, Bettina; Mlitz, Veronika; Fischer, Heinz; Tschachler, Erwin; Eckhart, Leopold


    The expression of filaggrin and its stepwise proteolytic degradation are critical events in the terminal differentiation of epidermal keratinocytes and in the formation of the skin barrier to the environment. Here, we investigated whether the evolutionary transition from a terrestrial to a fully aquatic lifestyle of cetaceans, that is dolphins and whales, has been associated with changes in genes encoding filaggrin and proteins involved in the processing of filaggrin. We used comparative genomics, PCRs and re-sequencing of gene segments to screen for the presence and integrity of genes coding for filaggrin and proteases implicated in the maturation of (pro)filaggrin. Filaggrin has been conserved in dolphins (bottlenose dolphin, orca and baiji) but has been lost in whales (sperm whale and minke whale). All other S100 fused-type genes have been lost in cetaceans. Among filaggrin-processing proteases, aspartic peptidase retroviral-like 1 (ASPRV1), also known as saspase, has been conserved, whereas caspase-14 has been lost in all cetaceans investigated. In conclusion, our results suggest that filaggrin is dispensable for the acquisition of fully aquatic lifestyles of whales, whereas it appears to confer an evolutionary advantage to dolphins. The discordant evolution of filaggrin, saspase and caspase-14 in cetaceans indicates that the biological roles of these proteins are not strictly interdependent. PMID:25739514

  10. Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: A role for the IAPs

    Dysregulation of apoptosis is involved in a wide spectrum of disease ranging from proliferative to degenerative disorders. An emerging area of study in apoptosis is the critical contribution of the endoplasmic reticulum (ER) in both mitochondrial and ER specific apoptosis pathways. Here we show that brefeldin A and tunicamycin-mediated ER stress lead to caspase-dependent apoptosis involving caspase-2. Confocal microscopy and subcellular fractionation indicate that caspase-2 is localized to the ER, and following ER stress, the processing of caspase-2 and -9 is an early event preceding the activation of caspase-3 and -7 and the cleavage of the caspase substrate poly(ADP-ribose) polymerase (PARP). Inhibition and silencing of either caspase-2 or caspase-9 suppress ER stress-induced apoptosis, as demonstrated by annexin V binding. Similarly, transduction with an adenovirus encoding either Inhibitors of Apoptosis (IAP) protein HIAP1/c-IAP2 or HIAP2/c-IAP1 also suppresses ER stress-induced apoptosis. However, among HIAP1, HIAP2 and XIAP, only HIAP2 binds and inhibits caspase-2. Our results thus indicate a novel mechanism by which HIAP2 can regulate ER-initiated apoptosis by modulating the activity of caspase-2

  11. Algorithmic Mechanism Design of Evolutionary Computation.

    Pei, Yan


    We consider algorithmic design, enhancement, and improvement of evolutionary computation as a mechanism design problem. All individuals or several groups of individuals can be considered as self-interested agents. The individuals in evolutionary computation can manipulate parameter settings and operations by satisfying their own preferences, which are defined by an evolutionary computation algorithm designer, rather than by following a fixed algorithm rule. Evolutionary computation algorithm designers or self-adaptive methods should construct proper rules and mechanisms for all agents (individuals) to conduct their evolution behaviour correctly in order to definitely achieve the desired and preset objective(s). As a case study, we propose a formal framework on parameter setting, strategy selection, and algorithmic design of evolutionary computation by considering the Nash strategy equilibrium of a mechanism design in the search process. The evaluation results present the efficiency of the framework. This primary principle can be implemented in any evolutionary computation algorithm that needs to consider strategy selection issues in its optimization process. The final objective of our work is to solve evolutionary computation design as an algorithmic mechanism design problem and establish its fundamental aspect by taking this perspective. This paper is the first step towards achieving this objective by implementing a strategy equilibrium solution (such as Nash equilibrium) in evolutionary computation algorithm. PMID:26257777

  12. Prokaryotic Caspase Homologs: Phylogenetic Patterns and Functional Characteristics Reveal Considerable Diversity

    Asplund-Samuelsson, Johannes; Bergman, Birgitta; Larsson, John


    Caspases accomplish initiation and execution of apoptosis, a programmed cell death process specific to metazoans. The existence of prokaryotic caspase homologs, termed metacaspases, has been known for slightly more than a decade. Despite their potential connection to the evolution of programmed cell death in eukaryotes, the phylogenetic distribution and functions of these prokaryotic metacaspase sequences are largely uncharted, while a few experiments imply involvement in programmed cell death. Aiming at providing a more detailed picture of prokaryotic caspase homologs, we applied a computational approach based on Hidden Markov Model search profiles to identify and functionally characterize putative metacaspases in bacterial and archaeal genomes. Out of the total of 1463 analyzed genomes, merely 267 (18%) were identified to contain putative metacaspases, but their taxonomic distribution included most prokaryotic phyla and a few archaea (Euryarchaeota). Metacaspases were particularly abundant in Alphaproteobacteria, Deltaproteobacteria and Cyanobacteria, which harbor many morphologically and developmentally complex organisms, and a distinct correlation was found between abundance and phenotypic complexity in Cyanobacteria. Notably, Bacillus subtilis and Escherichia coli, known to undergo genetically regulated autolysis, lacked metacaspases. Pfam domain architecture analysis combined with operon identification revealed rich and varied configurations among the metacaspase sequences. These imply roles in programmed cell death, but also e.g. in signaling, various enzymatic activities and protein modification. Together our data show a wide and scattered distribution of caspase homologs in prokaryotes with structurally and functionally diverse sub-groups, and with a potentially intriguing evolutionary role. These features will help delineate future characterizations of death pathways in prokaryotes. PMID:23185476

  13. A short caspase-3 isoform inhibits chemotherapy-induced apoptosis by blocking apoptosome assembly.

    Frédérique Végran

    Full Text Available Alternative splicing of caspase-3 produces a short isoform caspase-3s that antagonizes caspase-3 apoptotic activity. However, the mechanism of apoptosis inhibition by caspase-3s remains unknown. Here we show that exogenous caspase-3 sensitizes MCF-7 and HBL100 breast cancers cells to chemotherapeutic treatments such as etoposide and methotrexate whereas co-transfection with caspase-3s strongly inhibits etoposide and methotrexate-induced apoptosis underlying thus the anti-apoptotic role of caspase-3s. In caspase-3 transfected cells, lamin-A and α-fodrin were cleaved when caspase-3 was activated by etoposide or methotrexate. When caspase-3s was co-transfected, this cleavage was strongly reduced. Depletion of caspase-3 by RNA interference in HBL100 containing endogenous caspase-3s caused reduction in etoposide and methotrexate-induced apoptosis, whereas the depletion of caspase-3s sensitized cells to chemotherapy. In the presence of caspase-3s, a lack of interaction between caspase-3 and caspase-9 was observed. Immunoprecipitation assays showed that caspase-3s binds the pro-forms of caspase-3. This result suggested that the absence of interaction with caspase-9 when both variants of caspase-3 are present contribute to block the apoptosome assembly and inhibit apoptosis. These data support that caspases-3s negatively interferes with caspase-3 activation and apoptosis in breast cancer, and that it can play key roles in the modulation of response to chemotherapeutic treatments.

  14. Plant caspase-like proteases in plant programmed cell death

    Xu, Qixian; Zhang, Lingrui


    Programmed cell death (PCD) is a genetically-controlled disassembly of the cell. In animal systems, the central core execution switch for apoptotic PCD is the activation of caspases (Cysteine-containing Aspartate-specific proteases). Accumulating evidence in recent years suggests the existence of caspase-like activity in plants and its functional involvement in various types of plant PCD, although no functional homologs of animal caspases were identified in plant genome. In this mini-review, ...

  15. Hybridization of evolutionary algorithms

    Fister, Iztok; Mernik, Marjan; Brest, Janez


    Evolutionary algorithms are good general problem solver but suffer from a lack of domain specific knowledge. However, the problem specific knowledge can be added to evolutionary algorithms by hybridizing. Interestingly, all the elements of the evolutionary algorithms can be hybridized. In this chapter, the hybridization of the three elements of the evolutionary algorithms is discussed: the objective function, the survivor selection operator and the parameter settings. As an objective function...

  16. Allopurinol’s effect on caspase-3 and caspase-8 activity in hypoxic-ischemic newborn rats

    Kenan Özcan


    Full Text Available Aim: During reperfusion period of hypoxia-ischemia, cyclooxygenase and xanthine oxidase pathways are induced. A xanthine oxidase inhibitor, allopurinol has been shown to be neuroprotective in hypoxic- ischemic encephalopathy. Caspase-8 and caspase-3 have a key role in neuronal apoptosis. We aimed to test repeated doses of allopurinol’s effect on caspase-3 and caspase-8 activities in newborn rats with hypoxic-ischemic encephalopathy. Material and Method: Seven days old newborn rats were taken and there were 10 rats in each group. After Ethical Committee was approved (TIBDAM-25, rats were subjected to left carotid artery ligation and hypoxia (8% oxygen and 92% nitrogen for two and half hours. Hypoxic ischemic rats treated with 24 mg/kg allopurinol 30 minutes and 12 hours (AL48 group, and 30 minutes, 12 and 24 hours (AL72 group after hypoxic- ischemic insult. Twenty four hours after last dose, rats were decapitated. The others groups were sham and saline- treated hypoxic- ischemic (H-I group. Caspase- 3 and caspase- 8 activities were measured in both hemispheres.Results: There was no difference in caspase-3 and caspase-8 activities between right and left brain hemispheres in each group (p>0.05. Caspase-3 and caspase-8 activities were significantly lower in sham group when compared to H-I group, AL48 and AL72 groups (all of it, p=0.0001. Even though there were no difference activities of caspase- 3 and caspase- 8 between H-I group and AL48 group (p>0.05, activities of caspase- 3 and caspase- 8 in AL72 group were significantly lower than H-I group and AL48 group (respectively p= 0.0001, p=0.001. Conclusions: Decreased activities of caspase- 3 and caspase- 8 in AL72 group may suggest that totally dosage of 72 mg/kg allopurinol may be effective for reducing neuronal apoptosis in newborn rats with hypoxic- ischemic insult. (Turk Arch Ped 2013; 48: 48-52

  17. Pripper: prediction of caspase cleavage sites from whole proteomes

    Salmi Jussi


    Full Text Available Abstract Background Caspases are a family of proteases that have central functions in programmed cell death (apoptosis and inflammation. Caspases mediate their effects through aspartate-specific cleavage of their target proteins, and at present almost 400 caspase substrates are known. There are several methods developed to predict caspase cleavage sites from individual proteins, but currently none of them can be used to predict caspase cleavage sites from multiple proteins or entire proteomes, or to use several classifiers in combination. The possibility to create a database from predicted caspase cleavage products for the whole genome could significantly aid in identifying novel caspase targets from tandem mass spectrometry based proteomic experiments. Results Three different pattern recognition classifiers were developed for predicting caspase cleavage sites from protein sequences. Evaluation of the classifiers with quality measures indicated that all of the three classifiers performed well in predicting caspase cleavage sites, and when combining different classifiers the accuracy increased further. A new tool, Pripper, was developed to utilize the classifiers and predict the caspase cut sites from an arbitrary number of input sequences. A database was constructed with the developed tool, and it was used to identify caspase target proteins from tandem mass spectrometry data from two different proteomic experiments. Both known caspase cleavage products as well as novel cleavage products were identified using the database demonstrating the usefulness of the tool. Pripper is not restricted to predicting only caspase cut sites, but it gives the possibility to scan protein sequences for any given motif(s and predict cut sites once a suitable cut site prediction model for any other protease has been developed. Pripper is freely available and can be downloaded from Conclusions We have developed Pripper, a tool for

  18. Divergent modulation of neuronal differentiation by caspase-2 and -9.

    Giuseppa Pistritto

    Full Text Available Human Ntera2/cl.D1 (NT2 cells treated with retinoic acid (RA differentiate towards a well characterized neuronal phenotype sharing many features with human fetal neurons. In view of the emerging role of caspases in murine stem cell/neural precursor differentiation, caspases activity was evaluated during RA differentiation. Caspase-2, -3 and -9 activity was transiently and selectively increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated selective silencing of either caspase-2 (si-Casp2 or -9 (si-Casp9 was implemented in order to dissect the role of distinct caspases. The RA-induced expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM, microtubule associated protein-2 (MAP2 and tyrosine hydroxylase (TH mRNAs and proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells. During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a putative caspase substrate implicated in the regulation of the proneural bHLH MASH1 gene expression, was cleaved to a ∼100 kDa fragment. Sirt1 cleavage was markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated, but was not affected (still cleaved in si-Casp2 cells, despite a marked reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and occurred earlier in si-Casp2 cells, while was reduced at early time points during differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite functions during RA-induced NT2 neuronal differentiation. While caspase-9 activation is relevant for proper neuronal differentiation, likely through the fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA-induced neuronal differentiation of NT2 cells.

  19. 胱天蛋白酶(caspase)的前结构域%The Prodomain of Caspase

    梁赤周; 马志章


    @@ 胱天蛋白酶(caspase)是白细胞介素-1β转化酶(interleukin-1 β enzyme,ICE)家族的总称,Caspase(cysteine aspartate-special proteases)的含义是该类蛋白酶的活性部位为极为保守的半胱氨酸(cysteine)残基(取第一个字母“c”),又特异性切割底物的天冬氨酸,用“aspase”表示,简称caspase,该酶在细胞凋亡过程中起关键作用,是目前研究的热点.现已发现的caspase有14种,它们均以无活性的酶原的形式存在,包括一个N末端前结构域(prodomain)及大、小两个亚单位.

  20. Apo cytochrome c inhibits caspases by preventing apoptosome formation

    Caspases are cysteine proteases and potent inducers of apoptosis. Their activation and activity is therefore tightly regulated. There are several mechanisms by which caspases can be activated but one key pathway involves release of holo cytochrome c from mitochondria into the cytoplasm. Cytoplasmic holo cytochrome c binds to apoptotic protease activating factor-1 (Apaf-1), driving the formation of an Apaf-1 oligomer (the apoptosome) which in turn binds and activates caspase-9. Previously we showed that the apo form of cytochrome c (lacking heme) can bind Apaf-1 and block both holo-dependent caspase activation in cell extracts and Bax-induced apoptosis in cells. Here we tested the ability of apo cytochrome c to inhibit caspase-9 activation induced by recombinant Apaf-1. Furthermore, using purified proteins and size exclusion chromatography we show that apo cytochrome c prevents holo cytochrome c-dependent apoptosome formation

  1. Evolutionary Optimization The UGP Toolkit

    Sanchez, Ernesto; Squillero, Giovanni


    This book describes an award-winning evolutionary algorithm that outperformed experts and conventional heuristics in solving several industrial problems. It presents a discussion of the theoretical and practical aspects that enabled I GP (MicroGP) to autonomously find the optimal solution of hard problems, handling highly structured data, such as full-fledged assembly programs, with functions and interrupt handlers. For a practitioner, I GP is simply a versatile optimizer to tackle most problems with limited setup effort. The book is valuable for all who require heuristic problem-solving metho

  2. Evolutionary Rent-Seeking

    Hehenkamp, Burkhard; Leininger, Wolfgang; Possajennikov, Alex


    Tullock’s analysis of rent-seeking is reconsidered from an evolutionary point of view. We show that evolutionarily stable behavior in a rent-seeking contest differs from efficient rent-seeking behavior in a Nash equilibrium. We explore that implications of evolutionary stability for rent-seeking behavior and relate them to the well examined Nash equilibrium behavior. A most interesting result is an overdissipation law, which holds in evolutionary equilibrium.

  3. Overview: Evolutionary Algorithms

    Bartz-Beielstein, Thomas (Dr.); Mersmann, Olaf


    Evolutionary algorithm (EA) is an umbrella term used to describe population-based stochastic direct search algorithms that in some sense mimic natural evolution. Prominent representatives of such algorithms are genetic algorithms, evolution strategies, evolutionary programming, and genetic programming. On the basis of the evolutionary cycle, similarities and differences between these algorithms are described. We briefly discuss how EAs can be adapted to work well in case of multiple objective...

  4. Overview: Evolutionary Algorithms

    Bartz-Beielstein, Thomas (Dr.); Branke, Jürgen; Mehnen, Jörn; Mersmann, Olaf


    Evolutionary algorithm (EA) is an umbrella term used to describe population-based stochastic direct search algorithms that in some sense mimic natural evolution. Prominent representatives of such algorithms are genetic algorithms, evolution strategies, evolutionary programming, and genetic programming. On the basis of the evolutionary cycle, similarities and differences between these algorithms are described. We briefly discuss how EAs can be adapted to work well in case of multiple objective...

  5. Testing evolutionary convergence on Europa

    A major objective in solar system exploration is the insertion of appropriate biology-oriented experiments in future missions. We discuss various reasons for suggesting that this type of research be considered a high priority for feasibility studies and, subsequently, for technological development of appropriate melters and submersibles. Based on numerous examples, we argue in favour of the assumption that Darwin's theory is valid for the evolution of life anywhere in the universe. We have suggested how to obtain preliminary insights into the question of the distribution of life in the universe. Universal evolution of intelligent behaviour is at the end of an evolutionary pathway, in which evolution of ion channels in the membrane of microorganisms occurs in its early stages. Further, we have argued that a preliminary test of this conjecture is feasible with experiments on the Europan surface or ocean, involving evolutionary biosignatures (ion channels). This aspect of the exploration for life in the solar system should be viewed as a complement to the astronomical approach for the search of evidence of the later stages of the evolutionary pathways towards intelligent behaviour. (author)

  6. Evolutionary Algorithm Definition

    Nada M.A. AL-Salami


    Full Text Available Problem statement: Most resent evolutionary algorithms work under weak theoretical basis and thus, they are computationally expensive. Approach: This study discussed the use of new evolutionary algorithm for automatic programming, based on theoretical definitions of program behaviors. Evolutionary process adapted fixed and self-organized input-output specification of the problem, to evolve good finite state machine that efficiently satisfies these specifications. Results: The proposed algorithm enhanced evolutionary process by simultaneously solving multi-parts from the same problem. Conclusion: The probability that the algorithm will converge to the optimal solution was highly enhanced when decomposing the main problem into multi-part.

  7. Identification and Functional Characterization of Two Executioner Caspases in Crassostrea gigas

    Tao Qu; Baoyu Huang; Linlin Zhang; Li Li; Fei Xu; Wen Huang; Chunyan Li; Yishuai Du; Guofan Zhang


    Caspase-3 and caspase-7 are two key effector caspases that play important roles in apoptotic pathways that maintain normal tissue and organ development and homeostasis. However, little is known about the sequence, structure, activity, and function of effector caspases upon apoptosis in mollusks, especially marine bivalves. In this study, we investigated the possible roles of two executioner caspases in the regulation of apoptosis in the Pacific oyster Crassostrea gigas. A full-length caspase-...

  8. Evolutionary development of tensegrity structures.

    Lobo, Daniel; Vico, Francisco J


    Contributions from the emerging fields of molecular genetics and evo-devo (evolutionary developmental biology) are greatly benefiting the field of evolutionary computation, initiating a promise of renewal in the traditional methodology. While direct encoding has constituted a dominant paradigm, indirect ways to encode the solutions have been reported, yet little attention has been paid to the benefits of the proposed methods to real problems. In this work, we study the biological properties that emerge by means of using indirect encodings in the context of form-finding problems. A novel indirect encoding model for artificial development has been defined and applied to an engineering structural-design problem, specifically to the discovery of tensegrity structures. This model has been compared with a direct encoding scheme. While the direct encoding performs similarly well to the proposed method, indirect-based results typically outperform the direct-based results in aspects not directly linked to the nature of the problem itself, but to the emergence of properties found in biological organisms, like organicity, generalization capacity, or modularity aspects which are highly valuable in engineering. PMID:20619314

  9. Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7.

    Ruocco, Nadia; Varrella, Stefano; Romano, Giovanna; Ianora, Adrianna; Bentley, Matt G; Somma, Domenico; Leonardi, Antonio; Mellone, Stefano; Zuppa, Antonio; Costantini, Maria


    Diatoms are an important class of unicellular algae that produce bioactive secondary metabolites with cytotoxic activity collectively termed oxylipins, including polyunsaturated aldehydes (PUAs), hydroxyacids (HEPEs), oxo-acids and epoxyalcohols. Previous results showed that at higher concentrations, the PUA decadienal induced apoptosis on copepods and sea urchin embryos via caspase-3 activation; at lower concentrations decadienal affected the expression levels of the caspase-8 gene in embryos of the sea urchin Paracentrotus lividus. In the present work, we studied the effects of other common oxylipins produced by diatoms: two PUAs (heptadienal and octadienal) and four hydroxyacids (5-, 9- 11- and 15-HEPE) on P. lividus cell death and caspase activities. Our results showed that (i) at higher concentrations PUAs and HEPEs induced apoptosis in sea urchin embryos, detected by microscopic observation and through the activation of caspase-3/7 and caspase-8 measured by luminescent assays; (ii) at low concentrations, PUAs and HEPEs affected the expression levels of caspase-8 and caspase-3/7 (isolated for the first time here in P. lividus) genes, detected by Real Time qPCR. These findings have interesting implications from the ecological point of view, given the importance of diatom blooms in nutrient-rich aquatic environments. PMID:27130972

  10. Evolutionary cell biology: two origins, one objective.

    Lynch, Michael; Field, Mark C; Goodson, Holly V; Malik, Harmit S; Pereira-Leal, José B; Roos, David S; Turkewitz, Aaron P; Sazer, Shelley


    All aspects of biological diversification ultimately trace to evolutionary modifications at the cellular level. This central role of cells frames the basic questions as to how cells work and how cells come to be the way they are. Although these two lines of inquiry lie respectively within the traditional provenance of cell biology and evolutionary biology, a comprehensive synthesis of evolutionary and cell-biological thinking is lacking. We define evolutionary cell biology as the fusion of these two eponymous fields with the theoretical and quantitative branches of biochemistry, biophysics, and population genetics. The key goals are to develop a mechanistic understanding of general evolutionary processes, while specifically infusing cell biology with an evolutionary perspective. The full development of this interdisciplinary field has the potential to solve numerous problems in diverse areas of biology, including the degree to which selection, effectively neutral processes, historical contingencies, and/or constraints at the chemical and biophysical levels dictate patterns of variation for intracellular features. These problems can now be examined at both the within- and among-species levels, with single-cell methodologies even allowing quantification of variation within genotypes. Some results from this emerging field have already had a substantial impact on cell biology, and future findings will significantly influence applications in agriculture, medicine, environmental science, and synthetic biology. PMID:25404324

  11. Evolutionary humanoid robotics

    Eaton, Malachy


    This book examines how two distinct strands of research on autonomous robots, evolutionary robotics and humanoid robot research, are converging. The book will be valuable for researchers and postgraduate students working in the areas of evolutionary robotics and bio-inspired computing.

  12. Evolutionary Justification of Plagiarism

    Karpov, Alexander


    This paper provides evolutionary game theoretic model of plagiarism. The paper finds the relationship between author effort, publication value, and the frequency of plagiarism. There are two types of equilibria. Plagiarist-free equilibria are neutrally stable. The only evolutionary stable state is characterized by a positive share of plagiarists.

  13. Nominal aspect

    Rijkhoff, Jan


    In a general way the notion 'aspect' can be defined as the way in which a property or relation is represented in some dimension. Two kinds of aspect can be distinguished: verbal and nominal aspect. The study of verbal aspect has a long tradition, but nominal aspect has only been introduced recent......' (which will be analysed as nominal aspect markers below), (ii) noun-incorporation, and (iii) predicate nouns....

  14. Mechanismus der Inhibition und Aktivierung der Caspase-aktivierten DNase

    Kutscher, Daniel


    Der DNA Fragmentierungsfaktor DFF ist ein apoptotischer Protein Komplex, der aus den Untereinheiten CAD (Caspase aktivierte DNase) und ICAD (Inhibitor der Caspase aktivierten DNase) besteht. Da bis dato noch keine komplette Kristallstruktur des DFF Komplexes zur Verfügung steht, ist größtenteils immer noch unklar wie die beiden Untereinheiten, CAD und ICAD, auf molekularer Ebene miteinander interagieren. Der genaue Mechanismus der CAD Inhibition durch ICAD ist daher ebenso ungeklärt. In der v...

  15. The marine lipopeptide somocystinamide A triggers apoptosis via caspase 8

    Wrasidlo, Wolf; Mielgo, Ainhoa; Torres, Vicente A; Barbero, Simone; Stoletov, Konstantin; Suyama, Takashi L.; Klemke, Richard L.; Gerwick, William H.; Carson, Dennis A.; Stupack, Dwayne G.


    Screening for novel anticancer drugs in chemical libraries isolated from marine organisms, we identified the lipopeptide somocystinamide A (ScA) as a pluripotent inhibitor of angiogenesis and tumor cell proliferation. The antiproliferative activity was largely attributable to induction of programmed cell death. Sensitivity to ScA was significantly increased among cells expressing caspase 8, whereas siRNA knockdown of caspase 8 increased survival after exposure to ScA. ScA rapidly and efficien...

  16. SVM-based prediction of caspase substrate cleavage sites

    Wee, Lawrence JK; Tan, Tin Wee; Ranganathan, Shoba


    Background Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector...

  17. Discovery of Potent, Selective and Reversible Caspase-3 Inhibitors

    Han Yongxin; John Tam; Paul Tawa; Donald W. Nicholson; Robert J. Zamboni; André Giroux; John Colucci; Christopher I. Bayly; Daniel J. Mckay; Sophie Roy; Steve Xanthoudakis; John Vaillancourt; Dita M. Rasper


    Recent studies towards understanding the molecular mechanisms of apoptosis have revealed the importance of a group of cysteinyl aspartate specific proteases, the caspases, in the programmed cell death process (Hengartner, M.O. Nature 2000, 407, 770). Caspase-3, in particular,has been characterized as the dominant effector caspase involved in the proteolytic cleavage of a variety of protein substrates including cytoskeletal proteins, kinases and DNA repair enzymes during apoptosis (Nicholson, D. W. Cell Death Differ. 1999, 6, 1028). The development of potent and selective caspase-3 inhibitors has thus emerged as an attractive therapeutic target. In the presentation,the identification of a series of potent, selective and reversible non-peptidyl caspase-3 inhibitors containing a pyrazinone core (1) will be presented. SAR optimization at R1, R2, R3 and R4 led to the discovery of inhibitors such as 2 with excellent in vitro activities (IC50 against rh-caspase-3: 5 nM; IC50 against camptothecin induced apoptotic cell death in NT2 cells: 20 nM). Compounds such as 2 also displayed excellent in vivo activities in a number of animal models of acute injuries (see: Methot, N. et al, J. Exp. Med. 2004, 119, 199; Toulmond, S. et al, British J. Pharm. 2004, 141,689; Holtzman,D.M. et al, JBC, 2002, 277, 30128), and selected examples will be discussed during the presentation.

  18. Methylene Blue Inhibits Caspases by Oxidation of the Catalytic Cysteine.

    Pakavathkumar, Prateep; Sharma, Gyanesh; Kaushal, Vikas; Foveau, Bénédicte; LeBlanc, Andrea C


    Methylene blue, currently in phase 3 clinical trials against Alzheimer Disease, disaggregates the Tau protein of neurofibrillary tangles by oxidizing specific cysteine residues. Here, we investigated if methylene blue can inhibit caspases via the oxidation of their active site cysteine. Methylene blue, and derivatives, azure A and azure B competitively inhibited recombinant Caspase-6 (Casp6), and inhibited Casp6 activity in transfected human colon carcinoma cells and in serum-deprived primary human neuron cultures. Methylene blue also inhibited recombinant Casp1 and Casp3. Furthermore, methylene blue inhibited Casp3 activity in an acute mouse model of liver toxicity. Mass spectrometry confirmed methylene blue and azure B oxidation of the catalytic Cys163 cysteine of Casp6. Together, these results show a novel inhibitory mechanism of caspases via sulfenation of the active site cysteine. These results indicate that methylene blue or its derivatives could (1) have an additional effect against Alzheimer Disease by inhibiting brain caspase activity, (2) be used as a drug to prevent caspase activation in other conditions, and (3) predispose chronically treated individuals to cancer via the inhibition of caspases. PMID:26400108

  19. The calpain, caspase 12, caspase 3 cascade leading to apoptosis is altered in F508del-CFTR expressing cells.

    Mathieu Kerbiriou

    Full Text Available In cystic fibrosis (CF, the most frequent mutant variant of the cystic fibrosis transmembrane conductance regulator (CFTR, F508del-CFTR protein, is misfolded and retained in the endoplasmic reticulum (ER. We previously showed that the unfolded protein response (UPR may be triggered in CF. Since prolonged UPR activation leads to apoptosis via the calcium-calpain-caspase-12-caspase-3 cascade and because apoptosis is altered in CF, our aim was to compare the ER stress-induced apoptosis pathway between wild type (Wt and F508del-CFTR expressing cells. Here we show that the calcium-calpain-caspase-12-caspase-3 cascade is altered in F508del-CFTR expressing cells. We propose that this alteration is involved in the altered apoptosis triggering observed in CF.

  20. Evolutionary tree reconstruction

    Cheeseman, Peter; Kanefsky, Bob


    It is described how Minimum Description Length (MDL) can be applied to the problem of DNA and protein evolutionary tree reconstruction. If there is a set of mutations that transform a common ancestor into a set of the known sequences, and this description is shorter than the information to encode the known sequences directly, then strong evidence for an evolutionary relationship has been found. A heuristic algorithm is described that searches for the simplest tree (smallest MDL) that finds close to optimal trees on the test data. Various ways of extending the MDL theory to more complex evolutionary relationships are discussed.

  1. Computational intelligence synergies of fuzzy logic, neural networks and evolutionary computing

    Siddique, Nazmul


    Computational Intelligence: Synergies of Fuzzy Logic, Neural Networks and Evolutionary Computing presents an introduction to some of the cutting edge technological paradigms under the umbrella of computational intelligence. Computational intelligence schemes are investigated with the development of a suitable framework for fuzzy logic, neural networks and evolutionary computing, neuro-fuzzy systems, evolutionary-fuzzy systems and evolutionary neural systems. Applications to linear and non-linear systems are discussed with examples. Key features: Covers all the aspect

  2. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

    Selina Beasley


    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  3. When development matters: From evolutionary psychology to evolutionary developmental psychology

    Hernández Blasi, Carlos; Bjorklund, David F.; Gardiner, Amy K.


    This article presents evolutionary developmental psychology (EDP) as an emerging field of evolutionary psychology (EP). In describing the core tenets of both approaches and the differences between them, we emphasize the important roles that evolution and development have in understanding human behaviour. We suggest that developmental psychologists should pay more attention to evolutionary issues and, conversely, evolutionary psychologists should take development seriously ...

  4. Caspase 3 chemiluminiscence activity determination in apoptotic cells and design of Caspase 3 sensor

    Lišková, Marcela; Klepárník, Karel; Pazdera, P.; Foret, František

    Brno : Ústav analytické chemie AV ČR, v. v. i, 2012 - (Foret, F.; Křenková, J.; Guttman, A.; Klepárník, K.; Boček, P.), s. 344-348 ISBN 978-80-904959-1-3. [CECE 2012. International Interdisciplinary Meeting on Bioanalysis /9./. Brno (CZ), 01.11.2012-02.11.2012] R&D Projects: GA ČR(CZ) GAP301/11/2055; GA ČR GAP206/11/2377; GA MŠk(CZ) EE2.3.20.0182; GA ČR GA203/08/1680 Institutional research plan: CEZ:AV0Z40310501 Keywords : Caspase 3 * apoptosis * chemiluminescence * FRET Subject RIV: CB - Analytical Chemistry, Separation

  5. Caspase-2 protects against oxidative stress in vivo.

    Shalini, S; Puccini, J; Wilson, C H; Finnie, J; Dorstyn, L; Kumar, S


    Caspase-2 belongs to the caspase family of cysteine proteases with established roles in apoptosis. Recently, caspase-2 has been implicated in nonapoptotic functions including maintenance of genomic stability and tumor suppression. Our previous studies demonstrated that caspase-2 also regulates cellular redox status and delays the onset of several ageing-related traits. In the current study, we tested stress tolerance ability in caspase-2-deficient (Casp2(-/-)) mice by challenging both young and old mice with a low dose of the potent reactive oxygen species (ROS) generator, PQ that primarily affects lungs. In both groups of mice, PQ induced pulmonary damage. However, the lesions in caspase-2 knockout mice were consistently and reproducibly more severe than those in wild-type (WT) mice. Furthermore, serum interleukin (IL)-1β and IL-6 levels were higher in PQ-exposed aged Casp2(-/-) mice indicating increased inflammation. Interestingly, livers from Casp2(-/-) mice displayed karyomegaly, a feature commonly associated with ageing and aneuploidy. Given that Casp2(-/-) mice show impaired antioxidant defense, we tested oxidative damage in these mice. Protein oxidation significantly increased in PQ-injected old Casp2(-/-) mice. Moreover, FoxO1, SOD2 and Nrf2 expression levels were reduced and induction of superoxide dismutase (SOD) and glutathione peroxidase activity was not observed in PQ-treated Casp2(-/-) mice. Strong c-Jun amino-terminal kinase (JNK) activation was observed in Casp2(-/-) mice, indicative of increased stress. Together, our data strongly suggest that caspase-2 deficiency leads to increased cellular stress largely because these mice fail to respond to oxidative stress by upregulating their antioxidant defense mechanism. This makes the mice more vulnerable to exogenous challenges and may partly explain the shorter lifespan of Casp2(-/-) mice. PMID:25531319

  6. Adaptive Evolutionary Clustering

    Xu, Kevin S.; Kliger, Mark; Hero III, Alfred O.


    In many practical applications of clustering, the objects to be clustered evolve over time, and a clustering result is desired at each time step. In such applications, evolutionary clustering typically outperforms traditional static clustering by producing clustering results that reflect long-term trends while being robust to short-term variations. Several evolutionary clustering algorithms have recently been proposed, often by adding a temporal smoothness penalty to the cost function of a st...

  7. Evolutionary Theorizing in Economics

    Richard R. Nelson; Winter, Sidney G.


    This paper reviews the case for an evolutionary approach to problems of economic analysis, ranging from the details of individual firm behavior in the short run through industrial dynamics to the historical evolution of institutions and technologies. We draw upon a substantial body of recent research contributions. We characterize micro behavior as governed by skills and routines that are shaped by learning and selection. We then consider major areas of application of evolutionary thinking, i...

  8. Applications of Evolutionary Computation

    Squillero, Giovanni


    This book constitutes the refereed conference proceedings of the 18th International Conference on the Applications of Evolutionary Computation, EvoApplications 2015, held in Copenhagen, Spain, in April 2015, colocated with the Evo* 2015 events EuroGP, EvoCOP, and EvoMUSART. The 72 revised full papers presented were carefully reviewed and selected from 125 submissions. EvoApplications 2015 consisted of the following 13 tracks: EvoBIO (evolutionary computation, machine learning and data mining ...

  9. Collective behavior and evolutionary games - An introduction

    Perc, Matjaz


    This is an introduction to the special issue titled "Collective behavior and evolutionary games" that is in the making at Chaos, Solitons & Fractals. The term collective behavior covers many different phenomena in nature and society. From bird flocks and fish swarms to social movements and herding effects, it is the lack of a central planner that makes the spontaneous emergence of sometimes beautifully ordered and seemingly meticulously designed behavior all the more sensational and intriguing. The goal of the special issue is to attract submissions that identify unifying principles that describe the essential aspects of collective behavior, and which thus allow for a better interpretation and foster the understanding of the complexity arising in such systems. As the title of the special issue suggests, the later may come from the realm of evolutionary games, but this is certainly not a necessity, neither for this special issue, and certainly not in general. Interdisciplinary work on all aspects of collec...

  10. Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1

    Yong Zuo; Binggang Xiang; Jie Yang; Xuxu Sun; Yumei Wang; Hui Cang; Jing Yi


    Intracellular reactive oxygen species (ROS) are known to regulate apoptosis. Activation of caspase-9, the initial caspase in the mitochondrial apoptotic cascade, is closely associated with ROS, but it is unclear whether ROS regulate caspase-9 via direct oxidative modification. The present study aims to elucidate the molecular mechanisms by which ROS mediate caspase-9 activation. Our results show that the cellular oxidative state facilitates caspase-9 activation. Hydrogen peroxide treatment causes the activation of caspase-9 and apoptosis, and promotes an interaction between caspase-9 and apoptotic protease-activating factor 1 (Apaf-1) via disulfide formation. In addition, in an in vitro mitochondria-free system, the thiol-oxidant diamide promotes auto-cleavage of caspase-9 and the caspase-9/ Apaf-1 interaction by facilitating the formation of disulfide-linked complexes. Finally, a point mutation at C403 of caspase-9 impairs both H202-promoted caspase-9 activation and interaction with Apaf-1 through the abolition of disulfide formation. The association between cytochrome c and the C403S mutant is significantly weaker than that between cytochrome c and wild-type caspase-9, indicating that oxidative modification of caspase-9 contributes to apoptosome formation under oxidative stress. Taken together, oxidative modification of caspase-9 by ROS can mediate its interaction with Apaf-1, and can thus promote its auto-cleavage and activation. This mechanism may facilitate apoptosome formation and caspase-9 activation under oxidative stress.

  11. Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis.

    Coutermarsh-Ott, Sheryl L; Doran, John T; Campbell, Caroline; Williams, Tere M; Lindsay, David S; Allen, Irving C


    Toxoplasma gondii is an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection with T. gondii results in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilized Asc (-/-) and Casp11 (-/-) mice and infected these animals with T. gondii. Our data indicates that caspase-11 modulates the innate immune response to T. gondii through a mechanism which is distinct from that currently described for the canonical inflammasome. Asc (-/-) mice demonstrated increased disease pathogenesis during the acute phase of T. gondii infection, whereas Casp11 (-/-) mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis. PMID:27378827

  12. Extracting the evolutionary signal from genomes

    Dutilh, Bas E.


    Several methods to analyze aspects of evolution are developed, that depend on the availability of complete genomes. While I consistently find a phylogenetic signal using many approaches, a question that is winning concern is how these evolutionary relationships should be interpreted. Since Darwin’s idea about the tree-like structure of evolution, the dogma has been that evolution is mainly a vertical process, but recently, Doolittle pointed out that especially for prokaryotes, a tree may be i...

  13. Nitric oxide induces caspase activity in boar spermatozoa.

    Moran, J M; Madejón, L; Ortega Ferrusola, C; Peña, F J


    Nitric oxide (NO) is a highly reactive free radical that plays a key role in intra- and intercellular signaling. Production of radical oxygen species and an apoptotic-like phenomenon have recently been implicated in cryodamage during sperm cryopreservation. The objective of the present study was to evaluate the effect of sodium nitroprusside (SNP), an NO donor, on boar sperm viability. Semen samples were pooled from four boars that were routinely used for artificial insemination. Flow cytometry was used to compare semen incubated with SNP to control semen. Specifically, NO production was measured using the NO indicator dye diaminofluorescein diacetate, and caspase activity was determined using the permeable pan-caspase inhibitor Z-VAD linked to FITC. SNP induced a significant increase in the percentage of sperm cells showing caspase activity, from 9.3% in control samples to 76.2% in SNP-incubated samples (Pboar sperm damage. PMID:18433854

  14. Proteomics in evolutionary ecology.

    Baer, B; Millar, A H


    Evolutionary ecologists are traditionally gene-focused, as genes propagate phenotypic traits across generations and mutations and recombination in the DNA generate genetic diversity required for evolutionary processes. As a consequence, the inheritance of changed DNA provides a molecular explanation for the functional changes associated with natural selection. A direct focus on proteins on the other hand, the actual molecular agents responsible for the expression of a phenotypic trait, receives far less interest from ecologists and evolutionary biologists. This is partially due to the central dogma of molecular biology that appears to define proteins as the 'dead-end of molecular information flow' as well as technical limitations in identifying and studying proteins and their diversity in the field and in many of the more exotic genera often favored in ecological studies. Here we provide an overview of a newly forming field of research that we refer to as 'Evolutionary Proteomics'. We point out that the origins of cellular function are related to the properties of polypeptide and RNA and their interactions with the environment, rather than DNA descent, and that the critical role of horizontal gene transfer in evolution is more about coopting new proteins to impact cellular processes than it is about modifying gene function. Furthermore, post-transcriptional and post-translational processes generate a remarkable diversity of mature proteins from a single gene, and the properties of these mature proteins can also influence inheritance through genetic and perhaps epigenetic mechanisms. The influence of post-transcriptional diversification on evolutionary processes could provide a novel mechanistic underpinning for elements of rapid, directed evolutionary changes and adaptations as observed for a variety of evolutionary processes. Modern state-of the art technologies based on mass spectrometry are now available to identify and quantify peptides, proteins, protein

  15. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties

    Lawrence, C.P. [Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, University of Leicester, Leicester LE1 9HN (United Kingdom); Chow, S.C., E-mail: [School of Science, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, 46150 Selangor Darul Ehsan (Malaysia)


    The caspase inhibitors, benzyloxycarbony (Cbz)-l-Val-Ala-Asp (OMe)-fluoromethylketone (z-VAD-FMK) and benzyloxycarbonyl (Cbz)-Ile-Glu (OMe)-Thr-Asp (OMe)-FMK (z-IETD-FMK) at non-toxic doses were found to be immunosuppressive and inhibit human T cell proliferation induced by mitogens and IL-2 in vitro. Both caspase inhibitors were shown to block NF-κB in activated primary T cells, but have little inhibitory effect on the secretion of IL-2 and IFN-γ during T cell activation. However, the expression of IL-2 receptor α-chain (CD25) in activated T cells was inhibited by both z-VAD-FMK and z-IETD-FMK, whereas the expression of the early activated T cell marker, CD69 was unaffected. During primary T cell activation via the antigen receptor, both caspase-8 and caspase-3 were activated and processed to their respective subunits, but neither caspase inhibitors had any effect on the processing of these two caspases. In sharp contrast both caspase inhibitors readily blocked apoptosis and the activation of caspases during FasL-induced apoptosis in activated primary T cells and Jurkat T cells. Collectively, the results demonstrate that both z-VAD-FMK and z-IETD-FMK are immunosuppressive in vitro and inhibit T cell proliferation without blocking the processing of caspase-8 and caspase-3. -- Highlights: ► Caspase-8 and caspase-3 were activated during T cell activation and proliferation. ► T cell proliferation was blocked by caspase inhibitors. ► Caspase activation during T cell proliferation was not block by caspase inhibitors.

  16. Applications of evolutionary computation in image processing and pattern recognition

    Cuevas, Erik; Perez-Cisneros, Marco


    This book presents the use of efficient Evolutionary Computation (EC) algorithms for solving diverse real-world image processing and pattern recognition problems. It provides an overview of the different aspects of evolutionary methods in order to enable the reader in reaching a global understanding of the field and, in conducting studies on specific evolutionary techniques that are related to applications in image processing and pattern recognition. It explains the basic ideas of the proposed applications in a way that can also be understood by readers outside of the field. Image processing and pattern recognition practitioners who are not evolutionary computation researchers will appreciate the discussed techniques beyond simple theoretical tools since they have been adapted to solve significant problems that commonly arise on such areas. On the other hand, members of the evolutionary computation community can learn the way in which image processing and pattern recognition problems can be translated into an...

  17. Substrate-Induced Conformational Changes Occur in All Cleaved Forms of Caspase-6

    S Vaidya; E Velazquez-Delgado; G Abbruzzese; J Hardy


    Caspase-6 is an apoptotic cysteine protease that also governs disease progression in Huntington's and Alzheimer's diseases. Caspase-6 is of great interest as a target for treatment of these neurodegenerative diseases; however, the molecular basis of caspase-6 function and regulation remains poorly understood. In the recently reported structure of caspase-6, the 60's and 130's helices at the base of the substrate-binding groove extend upward, in a conformation entirely different from that of any other caspase. Presently, the central question about caspase-6 structure and function is whether the extended conformation is the catalytically competent conformation or whether the extended helices must undergo a large conformational rearrangement in order to bind substrate. We have generated a series of caspase-6 cleavage variants, including a novel constitutively two-chain form, and determined crystal structures of caspase-6 with and without the intersubunit linker. This series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure and function before and after substrate binding. Caspase-6 is inherently more stable than closely related caspases. Cleaved caspase-6 with both the prodomain and the linker present is the most stable, indicating that these two regions act in concert to increase stability, but maintain the extended conformation in the unliganded state. Moreover, these data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases.

  18. Teaching evolutionary biology

    Tidon Rosana


    Full Text Available Evolutionary Biology integrates several disciplines of Biology in a complex and interactive manner, where a deep understanding of the subject demands knowledge in diverse areas. Since this knowledge is often inaccessible to the majority of specialized professionals, including the teachers, we present some reflections in order to stimulate discussions aimed at the improvement of the conditions of education in this area. We examine the profile of evolutionary teaching in Brazil, based on questionnaires distributed to teachers in Secondary Education in the Federal District, on data provided by the "National Institute for Educational Studies and Research", and on information collected from teachers working in various regions of this country. Issues related to biological misconceptions, curriculum and didactic material are discussed, and some proposals are presented with the objective of aiding discussions aimed at the improvement of the teaching of evolutionary biology.

  19. Human nutrition: evolutionary perspectives.

    Barnicot, N A


    In recent decades, much new evidence relating to the ape forerunners of modern humans has come to hand and diet appears to be an important factor. At some stage, there must have been a transition from a largely vegetarian ape diet to a modern human hunting economy providing significant amounts of meat. On an even longer evolutionary time scale the change was more complex. The mechanisms of evolutionary change are now better understood than they were in Darwin's time, thanks largely to great advances in genetics, both experimental and theoretical. It is virtually certain that diet, as a major component of the human environment, must have exerted evolutionary effects, but researchers still have little good evidence. PMID:17393680

  20. Total Integrative Evolutionary Communication

    Nedergaard Thomsen, Ole; Brier, Søren


    and, on the other, Peircean biosemiotics. According to Cybersemiotics, language is primarily a creative process of total integrative evolutionary communication. It comprises three evolutionary stages: (1) biological reflexive languaging (the reflexive foundation of social coordination), (2......). In this inclusive hierarchy language games subsume the other stages, and thus human evolutionary communication is primarily a symbolic-conventional practice. It is intertwined with the practice of living, that is, with different life forms, including other forms of semiotic behavior. Together they form a coherent...... biological and socio-cultural practice. The basic “molecule” of the cybersemiotic model of human communication is a dyad between two linguistic cyborgs, alias natural language users. Single human communicators are thus “atoms”. They are hybrids between nature and nurture, manipulating all sorts...

  1. Evolutionary Statistical Procedures

    Baragona, Roberto; Poli, Irene


    This proposed text appears to be a good introduction to evolutionary computation for use in applied statistics research. The authors draw from a vast base of knowledge about the current literature in both the design of evolutionary algorithms and statistical techniques. Modern statistical research is on the threshold of solving increasingly complex problems in high dimensions, and the generalization of its methodology to parameters whose estimators do not follow mathematically simple distributions is underway. Many of these challenges involve optimizing functions for which analytic solutions a

  2. From computers to cultivation: reconceptualizing evolutionary psychology

    Louise eBarrett


    Full Text Available Does evolutionary theorizing have a role in psychology? This is a more contentious issue than one might imagine, given that as evolved creatures, the answer must surely be yes. The contested nature of evolutionary psychology lies not in our status as evolved beings, but in the extent to which evolutionary ideas add value to studies of human behaviour, and the rigour with which these ideas are tested. This, in turn, is linked to the framework in which particular evolutionary ideas are situated. While the framing of the current research topic places the brain-as-computer metaphor in opposition to evolutionary psychology, the most prominent school of thought in this field (born out of cognitive psychology, and often known as the Santa Barbara school is entirely wedded to the computational theory of mind as an explanatory framework. Its unique aspect is to argue that the mind consists of a large number of functionally specialized (i.e., domain-specific computational mechanisms, or modules (the massive modularity hypothesis. Far from offering an alternative to, or an improvement on, the current perspective, we argue that evolutionary psychology is a mainstream computational theory, and that its arguments for domain-specificity often rest on shaky premises. We then go on to suggest that the various forms of e-cognition (i.e., embodied, embedded, enactive represent a true alternative to standard computational approaches, with an emphasis on cognitive integration or the extended mind hypothesis in particular. We feel this offers the most promise for human psychology because it incorporates the social and historical processes that are crucial to human ‘mind-making’ within an evolutionarily-informed framework. In addition to linking to other research areas in psychology, this approach is more likely to form productive links to other disciplines within the social sciences, not least by encouraging a healthy pluralism in approach.

  3. Inner ear dysfunction in caspase-3 deficient mice

    Woo Minna


    Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

  4. Modulation of intracellular caspase machinery using organ culture approach

    Matalová, Eva; Fleischmannová, Jana; Norek, Adam; Míšek, Ivan

    Brno : Fyziologický ústav LF MU, 2007, 8P. [Fyziologické dny /83./. Brno (CZ), 06.02.2007-08.02.2007] Institutional research plan: CEZ:AV0Z50450515 Keywords : caspase machinery Subject RIV: EB - Genetics ; Molecular Biology

  5. Caspase-7 tooth germ and hair follicle development and maintenance

    Veselá, Barbora; Matalová, Eva

    Rome : ECDO, 2012. 257-257. [Euroconference from Death to Eternity /20./ and Training course on Concepts and Methods in Programmed Cell Death /9./. 14.09.2012-17.09.2012, Rome] R&D Projects: GA ČR(CZ) GAP502/12/1285 Institutional support: RVO:67985904 Keywords : caspase-7 * hair follicle * tooth germ Subject RIV: EA - Cell Biology

  6. Inhibition of caspases prevents ototoxic and ongoing hair cell death

    Matsui, Jonathan I.; Ogilvie, Judith M.; Warchol, Mark E.


    Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

  7. Programmed cell death in plants and caspase-like activities

    Gaussand, Gwénael Martial Daniel Jean-Marie


    The development of multicellular organisms involves an important balance between cell growth, cell division and cell death. In animals, programmed cell death (PCD) plays a key role by forming and deleting structures, controlling cell numbers and eliminating abnormal damaged cells. Caspases were foun

  8. Evolutionary Theories of Detection

    Fitch, J P


    Current, mid-term and long range technologies for detection of pathogens and toxins are briefly described in the context of performance metrics and operational scenarios. Predictive (evolutionary) and speculative (revolutionary) assessments are given with trade-offs identified, where possible, among competing performance goals.

  9. Part E: Evolutionary Computation


    Part E, Evolutionary Computation, edited by Professors Frank Neumann, Carsten Witt, Peter Merz, Carlos A. Coello Coello, Oliver Schütze, Thomas Bartz-Beielstein, Jörn Mehnen, and Günther Raidl, concerns the third fundamental element of what is traditionally being considered to be the core of Comp...

  10. Origins of evolutionary transitions

    Ellen Clarke


    An `evolutionary transition in individuality’ or `major transition’ is a transformation in the hierarchical level at which natural selection operates on a population. In this article I give an abstract (i.e. level-neutral and substrate-neutral) articulation of the transition process in order to precisely understand how such processes can happen, especially how they can get started.

  11. Identification and functional characterization of two executioner caspases in Crassostrea gigas.

    Tao Qu

    Full Text Available Caspase-3 and caspase-7 are two key effector caspases that play important roles in apoptotic pathways that maintain normal tissue and organ development and homeostasis. However, little is known about the sequence, structure, activity, and function of effector caspases upon apoptosis in mollusks, especially marine bivalves. In this study, we investigated the possible roles of two executioner caspases in the regulation of apoptosis in the Pacific oyster Crassostrea gigas. A full-length caspase-3-like gene named Cgcaspase-3 was cloned from C.gigas cDNA, encoding a predicted protein containing caspase family p20 and p10 domain profiles and a conserved caspase active site motif. Phylogenetic analysis demonstrated that both Cgcaspase-3 and Cgcaspase-1 may function as effector caspases clustered in the invertebrate branch. Although the sequence identities between the two caspases was low, both enzymes possessed executioner caspase activity and were capable of inducing cell death. These results suggested that Cgcaspase-3 and Cgcaspase-1 were two effector caspases in C. gigas. We also observed that nucleus-localized Cgcaspase-3, may function as a caspase-3-like protein and cytoplasm-localized Cgcaspase-1 may function as a caspase-7-like protein. Both Cgcaspase-3 and Cgcaspase-1 mRNA expression increased after larvae settled on the substratum, suggesting that both caspases acted in several tissues or organs that degenerated after oyster larvae settlement. The highest caspase expression levels were observed in the gills indicating that both effector caspases were likely involved in immune or metabolic processes in C. gigas.

  12. Recent Advances in Evolutionary Computation

    Xin Yao; Yong Xu


    Evolutionary computation has experienced a tremendous growth in the last decade in both theoretical analyses and industrial applications. Its scope has evolved beyond its original meaning of "biological evolution" toward a wide variety of nature inspired computational algorithms and techniques, including evolutionary, neural, ecological, social and economical computation, etc., in a unified framework. Many research topics in evolutionary computation nowadays are not necessarily "evolutionary". This paper provides an overview of some recent advances in evolutionary computation that have been made in CERCIA at the University of Birmingham, UK. It covers a wide range of topics in optimization, learning and design using evolutionary approaches and techniques, and theoretical results in the computational time complexity of evolutionary algorithms. Some issues related to future development of evolutionary computation are also discussed.


    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.


    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more oppo...

  14. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    The HPV-16 E6 and E6⁎ proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6⁎. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8

  15. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)


    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  16. Evolutionary computation in stochastic environments

    Schmidt, Christian


    This book develops efficient methods for the application of Evolutionary Algorithms on stochastic problems. To achieve this, procedures for statistical selection are systematically analyzed with respect to different measures and significantly improved. It is shown how to adapt one of the best procedures for the needs of Evolutionary Algorithms and Evolutionary operators for efficient implementation in stochastic environments are identified.

  17. Host-Dependent Trigger of Caspases and Apoptosis by Legionella pneumophila▿ †

    Santic, Marina; Asare, Rexford; Doric, Miljenko; Abu Kwaik, Yousef


    The Dot/Icm system of Legionella pneumophila triggers activation of caspase-3 during early stages of infection of human macrophages, but apoptosis is delayed until late stages of infection. During early stages of infection of mouse macrophages, the organism triggers rapid caspase-1-mediated cytotoxicity, which is mediated by bacterial flagellin. However, it is not known whether caspase-1 is triggered by L. pneumophila in human macrophages or whether caspase-3 is activated in permissive or non...

  18. Human development in an evolutionary perspective

    María Lucia Seidl-de-Moura


    Full Text Available This article presents an evolutionary perspectiveto the study of human development. Some generalassumptions for the study of development are discussedand the principal building blocks of evolutionarypsychology are presented. One of them isthat there is a universal human nature (which is modulatealso by particular conditions of each contextand the cognitive architecture of human beings isthe resulted of interactions between genes and environment.Based on those, and other assumptions,directions for the study of child development in anevolutionary stance are discussed, along with theconsiderations of context and development. Thus, itis assumed there is a relationship between phylogeniesand ontogenetic development (the ontogenesisneeds to be understood also as a product of evolution,considering the inseparability of biological,socio-cultural, cognitive emotional aspects thatconstitute this development. It has been concludedthat the evolutionary developmental psychologyhas scientific relevance because it broadens ourvision on human development.

  19. Evolutionary status of Entamoeba

    DONG Jiuhong; WEN Jianfan; XIN Dedong; LU Siqi


    In addition to its medical importance as parasitic pathogen, Entamoeba has aroused people's interest in its evolutionary status for a long time. Lacking mitochondrion and other intracellular organelles common to typical eukaryotes, Entamoeba and several other amitochondrial protozoans have been recognized as ancient pre-mitochondriate eukaryotes and named "archezoa", the most primitive extant eukaryotes. It was suggested that they might be living fossils that remained in a primitive stage of evolution before acquisition of organelles, lying close to the transition between prokaryotes and eukaryotes. However, recent studies revealed that Entamoeba contained an organelle, "crypton" or "mitosome", which was regarded as specialized or reductive mitochondrion. Relative molecular phylogenetic analyses also indicated the existence or the probable existence of mitochondrion in Entamoeba. Our phylogenetic analysis based on DNA topoisomerase II strongly suggested its divergence after some mitchondriate eukaryotes. Here, all these recent researches are reviewed and the evolutionary status of Entamoeba is discussed.

  20. Evolutionary constrained optimization

    Deb, Kalyanmoy


    This book makes available a self-contained collection of modern research addressing the general constrained optimization problems using evolutionary algorithms. Broadly the topics covered include constraint handling for single and multi-objective optimizations; penalty function based methodology; multi-objective based methodology; new constraint handling mechanism; hybrid methodology; scaling issues in constrained optimization; design of scalable test problems; parameter adaptation in constrained optimization; handling of integer, discrete and mix variables in addition to continuous variables; application of constraint handling techniques to real-world problems; and constrained optimization in dynamic environment. There is also a separate chapter on hybrid optimization, which is gaining lots of popularity nowadays due to its capability of bridging the gap between evolutionary and classical optimization. The material in the book is useful to researchers, novice, and experts alike. The book will also be useful...

  1. Evolutionary Design in Embryogeny

    Ashlock, Daniel

    In biology texts embryogeny is defined as "the development or production of an embryo." An embryo is a living creature in its first stage of life, from the fertilized egg cell through the initial development of its morphology and its chemical networks. The study of embryogeny is part of developmental biology [1, 2]. The reader may wonder why a book on evolutionary design should have a section on embryogeny. Computational embryogeny is the study of representations for evolutionary computation that mimic biological embryogeny. These representations contain analogs to the complex biological processes that steer a single cell to become a rose, a mouse, or a man. The advantage of using embryogenic representations is their richness of expression. A small seed of information can be expanded, through a developmental process, into a complex and potentially useful object. This richness of expression comes at a substantial price: the developmental process is sufficiently complex to be unpredictable.

  2. Expression and in vitro cleavage activity of anti-caspase-7 hammerhead ribozymes

    Wei Zhang; Qing Xie; Xia-Qiu Zhou; Shan Jiang; You-Xin Jin


    AIM: To prepare hammerhead ribozymes against mouse caspase-7 and identify their cleavage activityin vitro, in order to select a ribozyme with specific cleavage activity against mouse caspase-7 as a potential gene therapy for apoptosis-related diseases.METHODS: Anti-caspase-7 ribozymes targeting sites 333and 394 (named Rz333 and Rz394) were designed by computer software, and their DNA sequences encoding ribozymes were synthesized. Caspase-7 DNA sequence was acquired by RT-PCR. Ribozymes and caspase-7 DNA obtained byin vitro transcription were cloned into pBSKneo U6' and pGEM-T vectors, respectively. The cleavage activity of ribozymes against mouse caspase-7 was identified by cleavage experimentsin vitro.RESULTS: Rz333 and Rz394 were designed and their DNA sequences were synthesized respectively. The expression vector of caspase-7 and plasmids containing Rz333 and Rz394 were reconstructed successfully. Ribozymes and caspase-7 mRNA were expressed byin vitro transcription.In vitro cleavage experiment showed that 243-nt and 744-nt segments were produced after caspase-7 mRNA was mixed with Rz333 in equivalent, and the cleavage efficiency was 67.98%. No cleaved segment was observed when caspase-7 mRNA was mixed with Rz394.CONCLUSION: Rz333 can site-specific cleave mouse caspase-7 mRNA, and it shows a potential for gene therapy of apoptosis-related diseases by down-regulating gene expression of caspase-7.

  3. Evolutionary economics and psychology

    Witt, Ulrich


    Evolutionary economics is a paradigm for explaining the transformation of the economy. To achieve its goal, it needs being founded on a proper theory of economic behavior. The paper discusses these foundations. It is argued that the historical malleability of economic behavior is based on the interactions between innate behavior dispositions and adaptation mechanisms on the one hand and the limited, and always selective, cognitive and observational learning that contributes to an ever more ex...

  4. Learning in evolutionary environments

    Dosi, Giovanni; Marengo, Luigi; Fagiolo, Giogio


    The purpose of this work is to present a sort of short selective guide to an enormous and diverse literature on learning processes in economics. We argue that learning is an ubiquitous characteristic of most economic and social systems but it acquires even greater importance in explicitly evolutionary environments where: a) heterogeneous agents systematically display various forms of "bounded rationality"; b) there is a persistent appearance of novelties, both as exogenous shocks and as the r...

  5. Evolutionary game design

    Browne, Cameron


    The book describes the world's first successful experiment in fully automated board game design. Evolutionary methods were used to derive new rule sets within a custom game description language, and self-play trials used to estimate each derived game's potential to interest human players. The end result is a number of new and interesting games, one of which has proved popular and gone on to be commercially published.

  6. Evolutionary genomics of Entamoeba

    Weedall, Gareth D.; Hall, Neil


    Entamoeba histolytica is a human pathogen that causes amoebic dysentery and leads to significant morbidity and mortality worldwide. Understanding the genome and evolution of the parasite will help explain how, when and why it causes disease. Here we review current knowledge about the evolutionary genomics of Entamoeba: how differences between the genomes of different species may help explain different phenotypes, and how variation among E. histolytica parasites reveals patterns of population ...

  7. Evolutionary health psychology

    Dickins, Thomas E.


    For the last decade and a half the discipline of Evolutionary Psychology (EP) has been developing with great success. The first collection of significant papers was published in 1992 (Barkow et al.) and recently a landmark handbook has been produced summing the progress so far, as well as setting an agenda for future study (Buss, 2005). Unlike other areas within Psychology, EP extends its interest to all behaviours, rightly seeing them as part of an evolved phenotype, and health has not escap...

  8. Introduction to Evolutionary Algorithms

    Yu, Xinjie


    Evolutionary algorithms (EAs) are becoming increasingly attractive for researchers from various disciplines, such as operations research, computer science, industrial engineering, electrical engineering, social science, economics, etc. This book presents an insightful, comprehensive, and up-to-date treatment of EAs, such as genetic algorithms, differential evolution, evolution strategy, constraint optimization, multimodal optimization, multiobjective optimization, combinatorial optimization, evolvable hardware, estimation of distribution algorithms, ant colony optimization, particle swarm opti

  9. Evolutionary Aspects of Acaricide-Resistance Development in Spider Mites

    Masahiro (Mh. Osakabe


    Full Text Available Although the development of acaricide resistance in spider mites is a long-standing issue in agricultural fields, recent problems with acaricide resistance may be characterized by the development of complex- and/or multiresistance to acaricides in distinct classes. Such complexity of resistance is not likely to be a single mechanism. Pesticide resistance involves the microevolution of arthropod pests, and population genetics underlies the evolution. In this review, we address the genetic mechanisms of acaricide resistance evolution. We discuss genetic diversity and linkage of resistance genes, relationships between mite habitat and dispersal, and the effect of dispersal on population genetic structure and the dynamics of resistance genes. Finally, we attempt to present a comprehensive view of acaricide resistance evolution and suggest risks under globalization as well as possible approaches to managing acaricide resistance evolution or emergence.

  10. Evolutionary aspects of acoustic communication in Ribautodelphax planthoppers (Homoptera, Delphacidae).

    Winter, de A.J.


    Delphacidae (Homoptera), commonly referred to as planthoppers, are herbivores, which usually feed on grasses and sedges. During sexual behaviour males and females communicate by exchanging low-frequency vibrational signals, which are transmitted through the substrate, normally the host plant. This t

  11. The plant mitochondrial carrier family: functional and evolutionary aspects

    Ilka eHaferkamp; Stephan eSchmitz-Esser


    Mitochondria play a key role in respiration and energy production and are involved in multiple eukaryotic but also in several plant specific metabolic pathways. Solute carriers in the inner mitochondrial membrane connect the internal metabolism with that of the surrounding cell. Because of their common basic structure, these transport proteins affiliate to the mitochondrial carrier family (MCF). Generally, MCF proteins consist of six membrane-spanning helices, exhibit typical conserved domain...

  12. Ferric enterochelin transport in Yersinia enterocolitica: molecular and evolutionary aspects.

    Schubert, S; Fischer, D; Heesemann, J


    Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by fepC and fes, respectively. A frameshift mutation within the fepA gene led to expression of a truncated polypeptide of 40 kDa. The fepD, fepG, and fes genes of Y. enterocolitica were shown to complement corresponding E. coli mutants. Insertional mutagenesis of fepD or fes genes abrogates enterochelin-supported growth of Y. enterocolitica on iron-chelated media. In contrast to E. coli, the fep-fes gene cluster in Y. enterocolitica consists solely of genes required for uptake and utilization of enterochelin (fep) and not of enterochelin synthesis genes such as entF. By Southern hybridization, fepDGC and fes sequences could be detected in Y. enterocolitica biotypes IB, IA, and II but not in biotype IV strains, Yersinia pestis, and Yersinia pseudotuberculosis strains. According to sequence alignment data and the coherent structure of the Yersinia fep-fes gene cluster, we suggest early genetic divergence of ferrienterochelin uptake determinants among species of the family Enterobacteriaceae. PMID:10515929

  13. Ferric Enterochelin Transport in Yersinia enterocolitica: Molecular and Evolutionary Aspects

    Schubert, S.; Fischer, D; Heesemann, J


    Yersinia enterocolitica is well equipped for siderophore piracy, encompassing the utilization of siderophores such as ferrioxamine, ferrichrome, and ferrienterochelin. In this study, we report on the molecular and functional characterization of the Yersinia fep-fes gene cluster orthologous to the Escherichia coli ferrienterochelin transport genes (fepA, fepDGC, and fepB) and the esterase gene fes. In vitro transcription-translation analysis identified polypeptides of 30 and 35 kDa encoded by ...

  14. Evolutionary aspects of collective motility in pathogenic bacteria

    Deforet, Maxime; Xavier, Joao

    Pseudomonas aeruginosa is a pathogenic bacteria that can use its single polar flagellum to swim through liquids. It can move collectively over semisolid surfaces, a behavior called swarming. It can also settle and form surface-attached communities called biofilms that protect them from antibiotics. The transition from single motility (swimming) to collective motility (swarming) is biologically relevant as it enables exploring environments that a single bacterium cannot explore on its own. It is also clinically relevant since swarming and biofilm formation are thought to be antagonistic. We investigate the mechanisms of bacterial collective motility using a multidisciplinary approach that combines mathematical modeling, quantitative experiments, and microbial genetics. We aim to identify how these mechanisms may evolve under the selective pressure of population expansion, and consequently reinforce or hinder collective motility. In particular, we clarify the role of growth rate and motility in invasive populations.

  15. The ergot alkaloid gene cluster: Functional analyses and evolutionary aspects

    Lorenz, N.; Haarmann, T.; Pažoutová, Sylvie; Jung, M.; Tudzynski, P.


    Roč. 70, 15-16 (2009), s. 1822-1832. ISSN 0031-9422 Institutional research plan: CEZ:AV0Z50200510 Keywords : Claviceps purpurea * Ergot fungus * Ergot alkaloid gene cluster Subject RIV: EE - Microbiology, Virology Impact factor: 3.104, year: 2009

  16. Evolutionary aspects of acoustic communication in Ribautodelphax planthoppers (Homoptera, Delphacidae).

    Winter, de, A.J.


    Delphacidae (Homoptera), commonly referred to as planthoppers, are herbivores, which usually feed on grasses and sedges. During sexual behaviour males and females communicate by exchanging low-frequency vibrational signals, which are transmitted through the substrate, normally the host plant. This thesis deals with the acoustic behaviour of one planthopper genus, Ribautodelphax, where both male and females have been found to produce species-specific calls, which differ between species in temp...

  17. Asymmetric Evolutionary Games.

    McAvoy, Alex; Hauert, Christoph


    Evolutionary game theory is a powerful framework for studying evolution in populations of interacting individuals. A common assumption in evolutionary game theory is that interactions are symmetric, which means that the players are distinguished by only their strategies. In nature, however, the microscopic interactions between players are nearly always asymmetric due to environmental effects, differing baseline characteristics, and other possible sources of heterogeneity. To model these phenomena, we introduce into evolutionary game theory two broad classes of asymmetric interactions: ecological and genotypic. Ecological asymmetry results from variation in the environments of the players, while genotypic asymmetry is a consequence of the players having differing baseline genotypes. We develop a theory of these forms of asymmetry for games in structured populations and use the classical social dilemmas, the Prisoner's Dilemma and the Snowdrift Game, for illustrations. Interestingly, asymmetric games reveal essential differences between models of genetic evolution based on reproduction and models of cultural evolution based on imitation that are not apparent in symmetric games. PMID:26308326



    Objective To construct active recombinant cas pa ses-3 gene(r-caspases-3)eukaryotic expression plasmid and observe the apoptos is inducing activity of r-caspase-3 in pancreatic carcinoma cells. Methods pcDNA3.1(+)/r-caspase-3 was constructed and pan creatic carcinoma cells(PC-Ⅱ)were transfected with the pcDNA3.1(+)/r-caspases -3 by liposomes(LipofectAMINE).The expression of r-Caspase-3 mRNA in pancreat ic carcinoma cells was detected by reverse transcription process of the polymera se chain reaction(RT-PCR), and the signs of apoptosis were examined in pancreat ic carcinoma cells by the methods of the DNA electrophoresis and flow cytometry analysis(FACS).Results The sequence inserted in pBlueSKM/r-Caspase-3 p lasmid was coincident with that of the r-caspases-3. The evaluation result of pcDNA3.1(+)/r-caspases-3 through enzyme cutting was correct. A 894bp strap was observed by RT-PCR after pancreatic carcinoma cells being transfected with the pcDNA3.1(+)/r-caspases-3 by liposomes. No strap was found in control groups. A characteristic DNA ladder was observed in pancreatic carcinoma cells DNA elect r ophoresis, and transparent hypodiploid karyotype peak was found by FACS. Conclusion The plasmid of pcDNA3.1(+)/r-Caspase-3 was c onstructed successfully, the expression of r-Caspase-3 mRMA in pancreatic carc inoma cells was confirmed by RT-PCR, and pcDNA3.1(+)/r-Caspase-3 can induce a poptosis in pancreatic carcinoma cells.

  19. Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos).

    Schrantz, N; Auffredou, M T; Bourgeade, M F; Besnault, L; Leca, G; Vazquez, A


    Divalent cations, including Zinc and Manganese ions, are important modulators of cell activation. We investigated the ability of these two divalent cations to modulate apoptosis in human Burkitt lymphoma B cells line (Ramos). We found that Zinc (from 10 to 50 microM) inhibited Manganese-induced caspase-3 activation and apoptosis of Ramos cells. Higher concentration of Zinc (50 to 100 microM) did not prevent Manganese-mediated apoptosis but rather increased cell death among Ramos cells. This Zinc-mediated cell death was associated with apoptotic features such as cell shrinkage, the presence of phosphatidylserine residues on the outer leaflet of the cells, chromatin condensation, DNA fragmentation and decrease of mitochondrial transmembrane potential. Zinc-mediated apoptosis was associated with caspase-9 and caspase-3 activation as revealed by the appearance of active p35 fragment of caspase-9 and p19 and p17 of caspase-3 as well as in vivo cleavage of PARP and of a cell-permeable fluorogenic caspase-3 substrate (Phiphilux-G(1)D(2)). Both Zinc-mediated apoptosis and caspase-3 activation were prevented by the cell-permeable, broad-spectrum inhibitor of caspases (zVAD-fmk) or overexpression of bcl-2. In addition, we show that Zinc-induced loss of transmembrane mitochondrial potential is a caspase-independent event, since it is not modified by the presence of zVAD-fmk, which is inhibited by overexpression of bcl-2. These results indicate that depending on its concentration, Zinc can exert opposite effects on caspase-3 activation and apoptosis in human B lymphoma cells: concentrations below 50 microM inhibit caspase-3 activation and apoptosis whereas higher concentrations of Zinc activate a death pathway associated with apoptotic-like features and caspase-3 activation. PMID:11313717

  20. Possible involvement of caspase-6 and -7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells

    We recently reported that a broad-spectrum caspase inhibitor zVAD-fmk failed, while p38 inhibitor SB203580 succeeded, to prevent chromatin condensation and nuclear fragmentation induced by hypoxia in tube-forming HUVECs. In this study, we investigated the reasons for zVAD-fmk's inability to inhibit these morphological changes at the molecular level. The inhibitor effectively inhibited DNA ladder formation and activation of caspase-3 and -6, but it surprisingly failed to inhibit caspase-7 activation. On the other hand, SB203580 successfully inhibited all of these molecular events. When zLEHD-fmk, which specifically inhibits initiator caspase-9 upstream of caspase-3, was used, it inhibited caspase-3 activation but failed to inhibit caspase-6 and -7 activation. It also failed to inhibit hypoxia-induced chromatin condensation, nuclear fragmentation and DNA ladder formation. Taken together, our results indicate that, during hypoxia, caspase-7 is responsible for chromatin condensation and nuclear fragmentation while caspase-6 is responsible for DNA ladder formation

  1. Bioluminescence determination of active caspase-3 in single apoptotic cells

    Lišková, Marcela; Klepárník, Karel; Matalová, Eva; Hegrová, Jitka; Přikryl, Jan; Švandová, Eva; Foret, František


    Roč. 34, č. 12 (2013), s. 1772-1777. ISSN 0173-0835 R&D Projects: GA ČR GAP206/11/2377 Grant ostatní: GA ČR(CZ) GAP502/12/1285 Institutional support: RVO:68081715 ; RVO:67985904 Keywords : apoptosis * bioluminescence * caspase-3 Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.161, year: 2013

  2. Molar tooth development in caspase-3 deficient mice

    Matalová, Eva; Sharpe, P. T.; Lakhani, S. A.; Roth, K. A.; Flavell, R. A.; Šetková, Jana; Míšek, Ivan; Tucker, A. S.


    Roč. 50, 5 (2006), s. 491-497. ISSN 0214-6282 R&D Projects: GA AV ČR KJB500450503; GA MŠk OC B23.001 Grant ostatní: European Molecular Biology Organization ASTF195.00-05; NIH NS41962 Institutional research plan: CEZ:AV0Z50450515 Keywords : tooth development * dental apoptosis * caspase-3 mutant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.577, year: 2006

  3. Inactivation of the Human Vitamin D Receptor by Caspase-3

    Malloy, Peter J.; Feldman, David


    Calcitriol actions are mediated by the vitamin D receptor (VDR), a nuclear transcription factor of the steroid-retinoid-thyroid nuclear receptor gene superfamily. Calcitriol inhibits the growth of many cells including cancer cells by inducing cell cycle arrest. In some cancer cell lines, calcitriol also induces apoptosis. In the LNCaP prostate cancer cell line, induction of apoptosis and caspase-3/7 activities by staurosporine (STS) abolished [3H]1,25-dihydroxy vitamin D3 binding and VDR prot...

  4. Tumor promotion by caspase-resistant retinoblastoma protein

    Borges, Helena L.; Bird, Jeff; Wasson, Katherine; Cardiff, Robert D.; Varki, Nissi; Eckmann, Lars; Wang, Jean Y. J.


    The retinoblastoma (RB) protein regulates cell proliferation and cell death. RB is cleaved by caspase during apoptosis. A mutation of the caspase-cleavage site in the RB C terminus has been made in the mouse Rb-1 locus; the resulting Rb-MI mice are resistant to endotoxin-induced apoptosis in the intestine. The Rb-MI mice do not exhibit increased tumor incidence, because the MI mutation does not disrupt the Rb tumor suppressor function. In this study, we show that Rb-MI can promote the formation of colonic adenomas in the p53-null genetic background. Consistent with this tumor phenotype, Rb-MI reduces colorectal epithelial apoptosis and ulceration caused by dextran sulfate sodium. By contrast, Rb-MI does not affect the lymphoma phenotype of p53-null mice, in keeping with its inability to protect thymocytes and splenocytes from apoptosis. The Rb-MI protein is expressed and phosphorylated in the tumors, thereby inactivating its growth suppression function. These results suggest that RB tumor suppressor function, i.e., inhibition of proliferation, is inactivated by phosphorylation, whereas RB tumor promoting function, i.e., inhibition of apoptosis, is inactivated by caspase cleavage. PMID:16227443

  5. Caspase 6 has a protective role in SOD1(G93A) transgenic mice.

    Hogg, Marion C; Mitchem, Mollie R; König, Hans-Georg; Prehn, Jochen H M


    In amyotrophic lateral sclerosis (ALS), it has been suggested that the process of neurodegeneration starts at the neuromuscular junction and is propagated back along axons towards motor neurons. Caspase-dependent pathways are well established as a cause of motor neuron death, and recent work in other disease models indicated a role for caspase 6 in axonal degeneration. Therefore we hypothesised that caspase 6 may be involved in motor neuron death in ALS. To investigate the role of caspase 6 in ALS we profiled protein levels of caspase-6 throughout disease progression in the ALS mouse model SOD1(G93A); this did not reveal differences in caspase 6 levels during disease. To investigate the role of caspase 6 further we generated a colony with SOD1(G93A) transgenic mice lacking caspase 6. Analysis of the transgenic SOD1(G93A); Casp6(-/-) revealed an exacerbated phenotype with motor dysfunction occurring earlier and a significantly shortened lifespan when compared to transgenic SOD1(G93A); Casp6(+/+) mice. Immunofluorescence analysis of the neuromuscular junction revealed no obvious difference between caspase 6(+/+) and caspase 6(-/-) in non-transgenic mice, while the SOD1(G93A) transgenic mice showed severe degeneration compared to non-transgenic mice in both genotypes. Our data indicate that caspase-6 does not exacerbate ALS pathogenesis, but may have a protective role. PMID:26976329

  6. Role of Caspase and MMPs in Amniochorionic during PROM


    Objective To study the role of cysteine aspartic acid-specific protease-3 (caspase-3),matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metallo proteinase2 (TIMP-2) in human amniochorionic membranes during premature rupture of human fetal membranes (PROM).Methods Amniochorionic membranes were collected from the following groups of women: women with spontaneous PROM (n=8), women with normal labor in term after vaginal delivery(n=8) and women undergoing elective repeat cesarean section (C-section) before the onset of labor and who had no complications of pregnancy (n=8). Caspase-3 peptides were studies with use of immunohistochemistry. Messenger ribonucleic acid (mRNA) expression for MMP-2 and its specific inhibitors TIMP-2was studied with use of reverse transcriptase-polymerase chain reaction (RT-PCR).Results 1) The expressions of Caspase-3 peptides were 62.86 ± 3.83% in PROM group, 42.33 ±2.99% in vaginal delivery group, and 20.97 ± 2.94% in C- section group. There were statistically significant changes among the three groups (P<0.05).Immunohistochemistry demonstrated the presence of Caspase-3 in the amniotic epithelial cells and chorionic cytotrophoblast cells. 2) The expressions of MMP-2 were 84. 92 ±3.68% in PROM group, 32.65 ± 2.34% in vaginal delivery group, and 30.65 ±2.77% in C-section group. There were statistically significant changes between PROM and C-section group (P<0.05). 3) The expressions of TIMP-2 were 42. 01 ± 12.17% in PROM group, 73.01 ± 14.82% in vaginal delivery group, and 88.47 ± 6.51% in C- section group. There were statistically significant changes among the three groups (P<0.05).Conclusion Caspase-3 gene expressed more in PROM than in comparative group,which caused human fetal membranes cell apoptosis increased.The expression MMP-2increased and TIMP-2 dropped in PROM, which can increase the ECM decomposing.Cell apoptosis increased and extra cellular matrix degradation dropped, which may cause weakening of the

  7. Development of cell death-based method for the selectivity screening of caspase-1 inhibitors

    Chopra, Puneet; Gupta, Shashank; Dastidar, Sunanda G; Ray, Abhijit


    used for the selectivity screening of multiple caspases in a biologically relevant context in a single assay. In this study, we have developed an assay in which DNA fragmentation, a hallmark of apoptosis, of Jurkat cell line was examined post induction with etoposide in the presence or absence of...... belonging to caspase-1 family (1, 4 and 5) are not present in the Jurkat cells or might not be involved in the etoposide-induced DNA fragmentation. Since the inhibition of caspases 3, 8 and 9 is accompanied by the down regulation of the activity of a cascade of caspases (caspases 2, 6, 7, 9 and 10......Caspase-1 selective inhibitors are novel therapeutic agents for inflammatory diseases. Selectivity assays for caspases can be initiated with purified enzyme, making these assays very costly and time consuming. Therefore, there is a need to develop a fast and reliable cell-based assay, which can be...

  8. Mechanism of mitochondrial respiratory control in caspase-3 induced positive feed back loop in apoptosis


    Caspase-3 plays a central role in the execution of apoptosis. Besides many substrates of caspase-3, mitochondria seem to be one of the candidate targets in the apoptotic process. We evaluated the effects of caspase-3 on the isolated mitochondria in detail, and especially focused on the mechanism involved in mitochondrial functions, which were not fully assessed till now. Our results showed that recombinant caspase-3 induced the increase of superoxide production, the dissipation of mitochondrial membrane potential and rate increasing of mitochondrial state 4 respiration. Caspases inhibitor, z-VAD-fmk can inhibit these effects of caspase-3 on mitochondria. Bcl-xL and cyclosporin A were also shown to be able to inhibit these changes. These results suggested a possible mechanism in caspase-3 induced disruption of mitochondrial membrane barrier which formed a positive feedback loop in apoptosis.

  9. Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

    Hangping Yao; Xiajing Tang; Xueting Shao; Lei Feng; Nanping Wu; Ke Yao


    The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible molecular mechanisms involved. HLE cells (SRA01-04) were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide (10, 20 and 50μM). To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H2O2 for 18h, a high fraction of HLE cells underwent apoptosis, while in the presence of parthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H2O2 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation of caspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation of caspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.

  10. A Multiagent Simulation for Traffic Flow Management with Evolutionary Optimization

    Filipiak, Patryk


    A traffic flow is one of the main transportation issues in nowadays industrialized agglomerations. Configuration of traffic lights is among the key aspects in traffic flow management. This paper proposes an evolutionary optimization tool that utilizes multiagent simulator in order to obtain accurate model. Even though more detailed studies are still necessary, a preliminary research gives an expectation for promising results.

  11. Evolutionary Psychology: The Academic Debate

    Suplizio, Jean


    This dissertation examines the academic debate that surrounds the new field called "Evolutionary Psychology." Evolutionary psychology has emerged as the most popular successor theory to human sociobiology. Its proponents search for evolved psychological mechanisms and emphasize universal features of the human mind. My thesis is that in order to flourish evolutionary psychologists must engage other researchers on equal terms -- something they have not been doing. To show this, I examine the...

  12. Evolutionary algorithms in multiobjective problems

    Syomkin, A. M.; Zmitrovich, A. I.


    Many real-world problems involve two types of difficulties: 1) multiple, conflicting objectives and 2) a highly complex search space. Efficient evolutionary strategies have been developed to deal with both types of difficulties. Evolutionary algorithms possess several characteristics such as parallelism and robustness that make them preferable to classical optimization methods. In this work 1 conducted comparative studies among the well-known evolutionary algorithms based on NP-hard 0-1 multi...

  13. Binary Evolutionary Models

    Han, Z


    In this talk, we present the general principles of binary evolution and give two examples. The first example is the formation of subdwarf B stars (sdBs) and their application to the long-standing problem of ultraviolet excess (also known as UV-upturn) in elliptical galaxies. The second is for the progenitors of type Ia supernovae (SNe Ia). We discuss the main binary interactions, i.e., stable Roche lobe overflow (RLOF) and common envelope (CE) evolution, and show evolutionary channels leading to the formation of various binary-related objects. In the first example, we show that the binary model of sdB stars of Han et al. (2002, 2003) can reproduce field sdB stars and their counterparts, extreme horizontal branch (EHB) stars, in globular clusters. By applying the binary model to the study of evolutionary population synthesis, we have obtained an ``a priori'' model for the UV-upturn of elliptical galaxies and showed that the UV-upturn is most likely resulted from binary interactions. This has major implications...

  14. Distributed Evolutionary Computation using REST

    Castillo, P A; Mora, A M; Laredo, J L J; Romero, G; Rivas, V M; Merelo, J J


    This paper analises distributed evolutionary computation based on the Representational State Transfer (REST) protocol, which overlays a farming model on evolutionary computation. An approach to evolutionary distributed optimisation of multilayer perceptrons (MLP) using REST and language Perl has been done. In these experiments, a master-slave based evolutionary algorithm (EA) has been implemented, where slave processes evaluate the costly fitness function (training a MLP to solve a classification problem). Obtained results show that the parallel version of the developed programs obtains similar or better results using much less time than the sequential version, obtaining a good speedup.

  15. Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

    Flanagan, L; Meyer, M; Fay, J; Curry, S; Bacon, O; Duessmann, H; John, K; Boland, K C; McNamara, D A; Kay, E W; Bantel, H; Schulze-Bergkamen, H; Prehn, J H M


    Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a

  16. A genetic screen for modifiers of Drosophila caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes

    Ahnn Joohong


    Full Text Available Abstract Background Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of Dcp-1 gain-of-function (GF animals by screening promoter element- inserted Drosophila melanogaster lines (EP lines. Results We screened ~15,000 EP lines and identified 72 Dcp-1-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by Dcp-1 GF. Paradoxically, we found that over-expression of full-length Dcp-1 induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation. Conclusions We identified a number of Dcp-1 modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that Dcp-1 and autophagy-related genes influence each other will aid future

  17. EMT phenotype is induced by increased Src kinase activity via Src-mediated caspase-8 phosphorylation.

    Zhao, Yang; Li, XiaoJun; Sun, XiangFei; Zhang, YunFeng; Ren, Hong


    Caspase-8 governs multiple cell responses to the microenvironmental cues. However, its integration of "death-life" signalings remains elusive. In our study, the role of caspase-8-Src is well-established as a promoter for migration or metastasis in Casp8(+)Src(+) A549/H226 cells in vivo and in vitro. In particular for nude mice models, mice implanted with Casp8(+)Src(+) A459/H226 cells remarkably increased spontaneous tumor metastatic burden with a significant survival disadvantage. Additionally, we detect that Src-mediated caspase-8 phosphorylation stimulates Src phosphorylation at Tyr-416 via the linkage of Src SH2 domain with phosph-Tyr-380 site of caspase-8. In turn, activated Src can efficiently induce epithelial-mesenchymal transition (EMT) phenotypic features to promote tumor cells metastasis. Surprisingly, RXDLL motif deletion in the DEDa of caspase-8 attenuates tumor cell migration or metastasis via impairing the recruitment of caspase-8 into the cellular periphery where activated Src is subject to caspase-8 phosphorylation. Together, a simple model is that the peripherization of caspase-8 is well-poised to facilitate Src-mediated caspase-8 phosphrylation at Tyr-380, then binding of phospho-Tyr380 of caspase-8 to Src SH2 domain may maintain Src in an active conformation to induce EMT phenotype, a key step toward cancer metastasis. PMID:22508042

  18. A caspase active site probe reveals high fractional inhibition needed to block DNA fragmentation.

    Méthot, Nathalie; Vaillancourt, John P; Huang, JingQi; Colucci, John; Han, Yongxin; Ménard, Stéphane; Zamboni, Robert; Toulmond, Sylvie; Nicholson, Donald W; Roy, Sophie


    Apoptotic markers consist of either caspase substrate cleavage products or phenotypic changes that manifest themselves as a consequence of caspase-mediated substrate cleavage. We have shown recently that pharmacological inhibitors of caspase activity prevent the appearance of two such apoptotic manifestations, alphaII-spectrin cleavage and DNA fragmentation, but that blockade of the latter required a significantly higher concentration of inhibitor. We investigated this phenomenon through the use of a novel radiolabeled caspase inhibitor, [(125)I]M808, which acts as a caspase active site probe. [(125)I]M808 bound to active caspases irreversibly and with high sensitivity in apoptotic cell extracts, in tissue extracts from several commonly used animal models of cellular injury, and in living cells. Moreover, [(125)I]M808 detected active caspases in septic mice when injected intravenously. Using this caspase probe, an active site occupancy assay was developed and used to measure the fractional inhibition required to block apoptosis-induced DNA fragmentation. In thymocytes, occupancy of up to 40% of caspase active sites had no effect on DNA fragmentation, whereas inhibition of half of the DNA cleaving activity required between 65 and 75% of active site occupancy. These results suggest that a high and persistent fractional inhibition will be required for successful caspase inhibition-based therapies. PMID:15067000

  19. Caspase-dependent retinal ganglion cell apoptosis in the rat model of acute diabetes


    Background Neural apoptosis is generally believed to be mediated by two distinct pathways, caspase-dependant and caspase-independent pathways. This study investigated the apoptotic pathways involved in retinal ganglion ceils in acute diabetes in rats. Methods Diabetes was induced in male Wistar rats by a peritoneal injection of streptozotocin (STZ). Expression and localization of caspase-3 and apoptosis-inducing factor (AIF) proteins in the retina of diabetic rats was examined by Western blotting and immunohistochemistry analyses. Terminal transferase dUTP nick end labeling (TUNEL) assay and immunofluorescent staining specific for caspase-3 and AIF were applied to analyze for apoptosis of retinal ganglion cells. In addition, a caspase-3 inhibitor DEVD-CHO was injected intravitreally to further determine the apoptotic pathways of retinal ganglion cells triggered in acute diabetes. Results Two weeks after induction of diabetes, a significant increase in caspase-3 protein expression and localization occurred in the nerve fiber layer, ganglion cell layer, and inner plexiform layer of the retina. Four weeks after the onset of diabetes, the increase in caspase-3 expression was profound eight weeks postinduction of diabetes (P<0.05). Meanwhile, no AIF protein expression was detected in this study. In addition, intravitreal administration of the caspase-3 inhibitor DEVD-CHO reduced apoptosis of retinal ganglion cells by its direct inhibitory action on caspase-3. Conclusion Caspase-dependent apoptotic pathways may be the main stimulant of STZ-induced retinal ganglion cell apoptosis in acute diabetes.

  20. Ecstasy-Induced Caspase Expression Alters Following Ginger Treatment

    Asl, Sara Soleimani; Pourheydar, Bagher; Dabaghian, Fataneh; Nezhadi, Akram; ROOINTAN, AMIR; Mehdizadeh, Mehdi


    Introduction Exposure to 3-4, methylenedioxymethamphetamine (MDMA) leads to cell death. Herein, we studied the protective effects of ginger on MDMA- induced apoptosis. Methods 15 Sprague dawley male rats were administrated with 0, 10 mg/kg MDMA, or MDMA along with 100mg/kg ginger, IP for 7 days. Brains were removed to study the caspase 3, 8, and 9 expressions in the hippocampus by RT-PCR. Data was analyzed by SPSS 16 software using the one-way ANOVA test. Results MDMA treatment resulted in a ...

  1. interdisciplinary aspects

    Kempf, Davorin


    Summary: Symmetry is a universal principle in nature, sciences and arts. Generally speaking symmetry means that something looks the same when observed from certain different aspects. Symmetry is almost always broken – more or less, directly (in praxis) or spontaneously (in quantum field theory). There are discrete and continuous symmetries. Various forms of discrete symmetries – like bilateral, translative or rotative – associated with the field of arts, can also be recognized in our natu...

  2. 人难治性颞叶癫痫神经细胞凋亡与 Caspase 3,4的表达%Apoptosis and expression of Caspase 3 and Caspase 4 in neurocytes of refractory human temporal lobe epilepsy

    林若庭; 蔡若蔚; 张鹏飞; 林元相


    目的:观察人难治性颞叶癫痫(TLE)颞叶组织神经细胞凋亡及半胱氨酸天冬氨酸蛋白酶(Caspase )3和Caspase4的表达情况。方法免疫组化S-P染色法检测1993年1月至2008年5月福建医科大学病理学系与福建医科大学附属第一医院神经外科手术切除的30例人难治性颞叶癫痫组( TLE组)与10例脑外伤组(对照组)颞叶组织中神经细胞Caspase 3与Caspase 4的表达并分析其表达差异, TUNEL 法检测两组神经细胞的凋亡情况。结果 TLE 组颞叶组织神经细胞存在Caspase 3和Caspase 4的阳性表达且表达明显高于对照组( Caspase 3:0.69±0.10比0.26±0.05,t=12.905,P<0.01;Caspase 4:0.62±0.10比0.24±0.05,t=11.880,P<0.01),TLE组颞叶组织神经细胞凋亡指数(AI)较对照组显著增加(12.6±3.1比2.5±1.9,t=9.664,P<0.01)。结论人难治性TLE颞叶组织可能存在Caspase 3,Caspase 4转导的神经细胞凋亡。%Objective To study apoptosis and expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of refractory human temporal lobe epilepsy ( TLE).Methods The temporal tissue samples were obtained from 30 cases of refractory TLE ( TLE group) and 10 cases of brain trauma ( contrast group) between January 1993 and May 2008. The surgical specimens were paraffin-embedded samples from Department of Pathology of Fujian Medical University and Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University. S-P staining of immunohistochemistry was used to detect the expression of Caspase 3 and Caspase 4 in temporal lobe neurocytes of TLE group and contrast group.Their expression was then analyzed.The terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling ( TUNEL) staining was performed to visualize and analyze the neurocytes′apoptosis of two groups.Results The expression of Caspase 3 and Caspase 4 in neurocytes of TLE

  3. Spore: Spawning Evolutionary Misconceptions?

    Bean, Thomas E.; Sinatra, Gale M.; Schrader, P. G.


    The use of computer simulations as educational tools may afford the means to develop understanding of evolution as a natural, emergent, and decentralized process. However, special consideration of developmental constraints on learning may be necessary when using these technologies. Specifically, the essentialist (biological forms possess an immutable essence), teleological (assignment of purpose to living things and/or parts of living things that may not be purposeful), and intentionality (assumption that events are caused by an intelligent agent) biases may be reinforced through the use of computer simulations, rather than addressed with instruction. We examine the video game Spore for its depiction of evolutionary content and its potential to reinforce these cognitive biases. In particular, we discuss three pedagogical strategies to mitigate weaknesses of Spore and other computer simulations: directly targeting misconceptions through refutational approaches, targeting specific principles of scientific inquiry, and directly addressing issues related to models as cognitive tools.

  4. Complexity in Evolutionary Processes

    Darwin's principle of evolution by natural selection is readily casted into a mathematical formalism. Molecular biology revealed the mechanism of mutation and provides the basis for a kinetic theory of evolution that models correct reproduction and mutation as parallel chemical reaction channels. A result of the kinetic theory is the existence of a phase transition in evolution occurring at a critical mutation rate, which represents a localization threshold for the population in sequence space. Occurrence and nature of such phase transitions depend critically on fitness landscapes. The fitness landscape being tantamount to a mapping from sequence or genotype space into phenotype space is identified as the true source of complexity in evolution. Modeling evolution as a stochastic process is discussed and neutrality with respect to selection is shown to provide a major challenge for understanding evolutionary processes (author)

  5. Open Issues in Evolutionary Robotics.

    Silva, Fernando; Duarte, Miguel; Correia, Luís; Oliveira, Sancho Moura; Christensen, Anders Lyhne


    One of the long-term goals in evolutionary robotics is to be able to automatically synthesize controllers for real autonomous robots based only on a task specification. While a number of studies have shown the applicability of evolutionary robotics techniques for the synthesis of behavioral control, researchers have consistently been faced with a number of issues preventing the widespread adoption of evolutionary robotics for engineering purposes. In this article, we review and discuss the open issues in evolutionary robotics. First, we analyze the benefits and challenges of simulation-based evolution and subsequent deployment of controllers versus evolution on real robotic hardware. Second, we discuss specific evolutionary computation issues that have plagued evolutionary robotics: (1) the bootstrap problem, (2) deception, and (3) the role of genomic encoding and genotype-phenotype mapping in the evolution of controllers for complex tasks. Finally, we address the absence of standard research practices in the field. We also discuss promising avenues of research. Our underlying motivation is the reduction of the current gap between evolutionary robotics and mainstream robotics, and the establishment of evolutionary robotics as a canonical approach for the engineering of autonomous robots. PMID:26581015

  6. Evolutionary transitions in bacterial symbiosis

    Sachs, Joel L.; Skophammer, Ryan G.; Regus, John U.


    Diverse bacterial lineages form beneficial infections with eukaryotic hosts. The origins, evolution, and breakdown of these mutualisms represent important evolutionary transitions. To examine these key events, we synthesize data from diverse interactions between bacteria and eukaryote hosts. Five evolutionary transitions are investigated, including the origins of bacterial associations with eukaryotes, the origins and subsequent stable maintenance of bacterial mutualism with hosts, the captur...

  7. Topics of Evolutionary Computation 2001

    Ursem, Rasmus Kjær

    This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem......This booklet contains the student reports from the course: Topics of Evolutionary Computation, Fall 2001, given by Thiemo Krink, Rene Thomsen and Rasmus K. Ursem...

  8. Evolutionary Design of Boolean Functions

    WANG Zhang-yi; ZHANG Huan-guo; QIN Zhong-ping; MENG Qing-shu


    We use evolutionary computing to synthesize Boolean functions randomly. By using specific crossover and mutation operator in evolving process and modifying search space and fitness function, we get some high non-linearity functions which have other good cryptography characteristics such as autocorrelation etc. Comparing to other heuristic search techniques, evolutionary computing approach is more effective because of global search strategy and implicit parallelism.

  9. Chaos Synthesis by Evolutionary Algorithms

    Zelinka, I.; Chen, G.; Čelikovský, Sergej

    Berlin : Springer-Verlag, 2010 - (Zelinka, I.; Čelikovský, S.; Richter, H.; Chen, G.), s. 345-382 ISBN 978-3-642-10706-1. - (Studies in Computational Intelligence. 267) Institutional research plan: CEZ:AV0Z10750506 Keywords : chaos synthesis * evolutionary algorithms * self organizingmigrating * evolutionary computing Subject RIV: BC - Control Systems Theory

  10. Evolutionary Explanations of Eating Disorders

    Igor Kardum


    Full Text Available This article reviews several most important evolutionary mechanisms that underlie eating disorders. The first part clarifies evolutionary foundations of mental disorders and various mechanisms leading to their development. In the second part selective pressures and evolved adaptations causing contemporary epidemic of obesity as well as differences in dietary regimes and life-style between modern humans and their ancestors are described. Concerning eating disorders, a number of current evolutionary explanations of anorexia nervosa are presented together with their main weaknesses. Evolutionary explanations of eating disorders based on the reproductive suppression hypothesis and its variants derived from kin selection theory and the model of parental manipulation were elaborated. The sexual competition hypothesis of eating disorder, adapted to flee famine hypothesis as well as explanation based on the concept of social attention holding power and the need to belonging were also explained. The importance of evolutionary theory in modern conceptualization and research of eating disorders is emphasized.

  11. p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin

    Ehrnhoefer, Dagmar E; Skotte, Niels H; Ladha, Safia;


    as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A....... Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated...... increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase...

  12. Design and Synthesis of a Novel Peptidomimetic Inhibitor of Caspase-3


    Caspases, a family of cysteine proteases, comprise of highly homologous enzymes that play an important role in apoptotic cell death. Caspase-3 shows key functions in apoptosis, mediating apoptotic cascade from the intrinsic and extrinsic activation pathways. Therefore, caspase-3 is an attractive target for therapeutic intervention. For instance,inhibitors of caspase-3 have been described as promising cardioprotectants, neuroprotectants and antiarthritic agents.A novel peptidomimetic inhibitor of caspase-3, has been designed, which still has the properties of a reversible inhibitor, while the P1 site at the C-terminal remains, and only L-amino acid has been replaced by D-amino acid. Also presented here is the synthesis of the inhibitor and its inhibitory activity against caspase-3, which was tested by the fluorescent activity assay.

  13. The evolutionary genetics of canalization.

    Flatt, Thomas


    Evolutionary genetics has recently made enormous progress in understanding how genetic variation maps into phenotypic variation. However why some traits are phenotypically invariant despite apparent genetic and environmental changes has remained a major puzzle. In the 1940s, Conrad Hal Waddington coined the concept and term "canalization" to describe the robustness of phenotypes to perturbation; a similar concept was proposed by Waddington's contemporary Ivan Ivanovich Schmalhausen. This paper reviews what has been learned about canalization since Waddington. Canalization implies that a genotype's phenotype remains relatively invariant when individuals of a particular genotype are exposed to different environments (environmental canalization) or when individuals of the same single- or multilocus genotype differ in their genetic background (genetic canalization). Consequently, genetic canalization can be viewed as a particular kind of epistasis, and environmental canalization and phenotypic plasticity are two aspects of the same phenomenon. Canalization results in the accumulation of phenotypically cryptic genetic variation, which can be released after a "decanalizing" event. Thus, canalized genotypes maintain a cryptic potential for expressing particular phenotypes, which are only uncovered under particular decanalizing environmental or genetic conditions. Selection may then act on this newly released genetic variation. The accumulation of cryptic genetic variation by canalization may therefore increase evolvability at the population level by leading to phenotypic diversification under decanalizing conditions. On the other hand, under canalizing conditions, a major part of the segregating genetic variation may remain phenotypically cryptic; canalization may therefore, at least temporarily, constrain phenotypic evolution. Mechanistically, canalization can be understood in terms of transmission patterns, such as epistasis, pleiotropy, and genotype by environment

  14. Evolutionary Design of Controlled Structures

    Masters, Brett P.; Crawley, Edward F.


    Basic physical concepts of structural delay and transmissibility are provided for simple rod and beam structures. Investigations show the sensitivity of these concepts to differing controlled-structures variables, and to rational system modeling effects. An evolutionary controls/structures design method is developed. The basis of the method is an accurate model formulation for dynamic compensator optimization and Genetic Algorithm based updating of sensor/actuator placement and structural attributes. One and three dimensional examples from the literature are used to validate the method. Frequency domain interpretation of these controlled structure systems provide physical insight as to how the objective is optimized and consequently what is important in the objective. Several disturbance rejection type controls-structures systems are optimized for a stellar interferometer spacecraft application. The interferometric designs include closed loop tracking optics. Designs are generated for differing structural aspect ratios, differing disturbance attributes, and differing sensor selections. Physical limitations in achieving performance are given in terms of average system transfer function gains and system phase loss. A spacecraft-like optical interferometry system is investigated experimentally over several different optimized controlled structures configurations. Configurations represent common and not-so-common approaches to mitigating pathlength errors induced by disturbances of two different spectra. Results show that an optimized controlled structure for low frequency broadband disturbances achieves modest performance gains over a mass equivalent regular structure, while an optimized structure for high frequency narrow band disturbances is four times better in terms of root-mean-square pathlength. These results are predictable given the nature of the physical system and the optimization design variables. Fundamental limits on controlled performance are discussed

  15. Ekspresi Bcl-2 dan Caspase-3 Pascapaparan Hipoksia Hipobarik Intermiten

    Achmad Hidayat


    Full Text Available Intermittent hypobaric hypoxia often suffered by cabin crew due to the fact that they are breathing lower pressured air inside the plane cabin. Human body will adapt by binding more oxygen and reducing hypoxia effect. Mitochondria function will be irritated by hypoxia which affect, outer mithochondrial membrane permeability due to decrease of Bcl-2 protein. Later on if hypoxia continues mitochondrial membrane will leaked cytocrome-c will released and apoptotic pathway will occur. The purpose of this study was to analyze Bcl-2 protein as antiapoptosis and caspase-3 as apoptosis indicator of intermittent hypobaric hypoxia exposure. Experimental study >was subjected to Spraque Dawley male mice during January–April 2010 by exposing them to several intermittent hypobaric hypoxias (one to four treatment in an interval of one week. Protein expression on mice heart cell were detected by immunohistochemistry in the Department of Pathology Anatomy Padjadjaran University-RS Dr. Hasan Sadikin Bandung and western blot methods in Department Biomolecullar Indonesia University Jakarta. Bcl-2 protein expressions increased according with the frequency of intermittent hypobaric hypoxia exposures while a reverse trend was found for caspase-3 protein expressions (rs=-0.448, p=0.013. From the study it can be concluded that apoptosis will be decreased as a result of intermittent hypobaric hypoxia exposures, which occurred from natural adaptation mechanism indicated by decrease of cell apoptosis and cardio protective effect will be emerged.

  16. TNF-alpha-induced mitochondrial alterations in human T cells requires FADD and caspase-8 activation but not RIP and caspase-3 activation.

    Shakibaei, Mehdi; Sung, Bokyung; Sethi, Gautam; Aggarwal, Bharat B


    Although much is known about how TNF-alpha induces apoptosis in the presence of inhibitors of protein synthesis, little is known about how it induces apoptosis without these inhibitors. In this report we investigated temporal sequence of events induced by TNF-alpha in the absence of protein synthesis. Regardless of whether we measured the effects by plasma membrane phosphotidylserine accumulation, by DNA strand breaks, or activation of caspases, significant changes were observed only between 12-24 h of TNF-alpha treatment. One of the earliest changes observed after TNF-alpha treatment was mitochondrial swelling at 10 min; followed by cytochrome c and Smac release at 10-30 min, and then heterochromatin clumping occurred at 60 min. While genetic deletion of receptor-interaction protein (RIP) had no effect on TNF-alpha-induced mitochondrial damage, deletion of Fas-associated death domain (FADD) abolished the TNF-induced mitochondrial swelling. Since pan-caspase inhibitor z-VAD-fmk abolished the TNF-alpha-induced mitochondrial changes, z-DEVD-fmk, an inhibitor of caspase-3 had no effect, suggesting that TNF-alpha-induced mitochondrial changes or cytochrome c and Smac release requires caspase-8 but not caspase-3 activation. Overall, our results indicated that mitochondrial changes are early events in TNF-alpha-induced apoptosis and that these mitochondrial changes require recruitment of FADD and caspase-8 activation, but not caspase-3 activation or RIP recruitment. PMID:20136500

  17. Differential Activity of Caspase-3 Regulates Susceptibility of Lung and Breast Tumor Cell Lines to Paclitaxel

    Odonkor, Charles Amoatey; Achilefu, Samuel


    Recent development of tumor resistance to paclitaxel presents a major problem to cancer treatment. An unsettled controversy in the cancer chemotherapy field, however, is whether caspases play a prominent role in paclitaxel-induced death in tumors. Previous studies suggest that cleavage of caspase-3 is not instrumental for the execution of death in tumors treated with paclitaxel, while other reports indicate that caspase-dependent pathways may be critical for paclitaxel cytotoxicity. In this s...

  18. Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates

    Cieplak, Piotr


    Caspases are enzymes belonging to a conserved family of cysteine-dependent aspartic-specific proteases that are involved in vital cellular processes and play a prominent role in apoptosis and inflammation. Determining all relevant protein substrates of caspases remains a challenging task. Over 1500 caspase substrates have been discovered in the human proteome according to published data and new substrates are discovered on a daily basis. To aid the discovery process we devel...

  19. Pharmacophore Modeling and Docking Studies on Some Nonpeptide-Based Caspase-3 Inhibitors

    Simant Sharma; Arijit Basu; Agrawal, R K


    Neurodegenerative disorders are major consequences of excessive apoptosis caused by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has become a validated therapeutic approach for neurodegenerative disorders. We performed pharmacophore modeling on some synthetic derivatives of caspase-3 inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in the common pharmacophore hypothesis AAHRR.6 which might be responsible for the biological activity: tw...

  20. Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation

    Bergsbaken, Tessa; Fink, Susan L.; den Hartigh, Andreas B.; Loomis, Wendy P.; Cookson, Brad T.


    Activation of caspase-1 leads to pyroptosis, a program of cell death characterized by cell lysis and inflammatory cytokine release. Caspase-1 activation triggered by multiple NLRs (NLRC4, NLRP1b, or NLRP3) leads to loss of lysosomes via their fusion with the cell surface, or lysosome exocytosis. Active caspase-1 increased cellular membrane permeability and intracellular calcium levels, which facilitated lysosome exocytosis and release of host antimicrobial factors and microbial products. Lyso...

  1. Estrous sheep serum enables in vitro capacitation of ram spermatozoa while preventing caspase activation.

    Del Olmo, E; García-Álvarez, O; Maroto-Morales, A; Ramón, M; Jiménez-Rabadán, P; Iniesta-Cuerda, M; Anel-Lopez, L; Martinez-Pastor, F; Soler, A J; Garde, J J; Fernández-Santos, M R


    Estrous sheep serum (ESS) is considered the most efficient agent for in vitro capacitation of ram spermatozoa. We have explored the relationship between caspase activation and capacitation in ram. Semen samples from 17 rams were cryopreserved. In vivo fertility was evaluated after intrauterine artificial insemination. Samples were submitted to four treatments: control, ESS (10%), caspase inhibitor (Z-VAD-FMK), and estrous ewe serum plus caspase inhibitor (I + E). Sperm samples were incubated for 30 minutes at 38.5 °C and 5% CO2 and analyzed with flow cytometry for mitochondrial membrane potential (MitoTracker deep red), sperm viability and apoptosis-like changes (YO-PRO-1/propidium iodide), acrosomal status (peanut agglutinin-fluorescein isothiocyanate), membrane fluidity (merocyanine 540), and caspase activity (Vybrant FAM kits for polycaspases, caspase-8, and caspases 3-7). Estrous sheep serum induced changes compatible with capacitation, doubling the proportion of viable spermatozoa with increased merocyanine 540 and increasing YO-PRO-1(+) and acrosome-reacted spermatozoa (P < 0.05). Incubation increased the proportion of spermatozoa with activated caspases (P < 0.05), which was abolished by the treatments. We detected a simultaneous decrease in the proportion of the viable and caspase(-) spermatozoa after the incubation, which was prevented by the presence of estrous ewe serum (P < 0.05). The analysis of caspases 3/7 and 8 resulted in less marked differences. Fertility was positively related to viability and inactivated caspases and negatively to viable-capacitated spermatozoa and active caspases. In vitro induction of capacitation in thawed ram spermatozoa by using ESS suggests a downregulation in apoptotic pathways. However, males with the lowest fertility showed parameters similar to high-fertility males, suggesting that other factors were involved apart from capacitation and/or caspase activation. PMID:26474680

  2. Expression of second mitochondria-derived activator of caspases, X-linked inhibitor of apoptosis protein, and caspase-3 in pituitary adenomas

    Dong Li; Gang Huo; Liang Wang; Qinglin Feng; Maoyuan Tang


    Studies concerning correlations between pituitary adenomas and cell apoptosis have mainly focused on upstream apoptosis signaling, but seldom on downstream mediators. In the present study, second mitochondria-derived activator of caspases (Smac), X-linked inhibitor of apoptosis protein (XIAP), and caspase-3 protein were qualitatively analyzed using imrnunohistochemistry, and quantified by western blot. Smac, XIAP, and caspase-3 mRNA expressions were detected by reverse transcription-PCR. Results showed that XIAP protein and mRNA expressions were greater in the invasive pituitary adenoma group compared with the noninvasive pituitary adenoma group. However, Smac and caspase-3 protein and mRNA expressions were lower in the invasive pituitary adenoma group compared with the noninvasive pituitary adenoma group. In the invasive pituitary adenomas, Smac expression was positively correlated with caspase-3 protein and mRNA expression (Protein: r=0.55, P<0.01;mRNA: r=0.50, P<0.01). Smac and caspase-3 expressions were negatively correlated with XIAP protein and mRNA expression (Protein: r=-0.56, -0.64, P<0.01;mRNA:r=-0.69,-0.67,P<0.01). However, no significant differences in correlation among Srnac, XIAP, and caspase-3 were detectable in noninvasive pituitary adenomas. These data indicated that high expression of XIAP and low expression of Smac and caspase-3 suppressed cell apoptosis and led to enhanced invasiveness of pituitary adenomas. Thus, Smac, XIAP, and caspase-3 may be useful markers in determining the invasive behavior of pituitary adenomas.

  3. Regulation of NF-κB signaling by caspases and MALT1 paracaspase

    Jens Staal; Tine Bekaert; Rudi Beyaert


    Caspases are intracellular proteases that are best known for their function in apoptosis signaling.It has become evident that many caspases also function in other signaling pathways that propagate cell proliferation and inflammation,but studies on the inflammatory function of caspases have mainly been limited to caspase-1-mediated cytokine processing.Emerging evidence,however,indicates an important contribution of caspases as mediators or regulators of nuclear factor-κB(NF-κB)signaling,which plays a key role in inflammation and immunity.Much still needs to be learned about the mechanisms that govern the activation and regulation of NF-κB by caspases,and this review provides an update of this area.Whereas apoptosis signaling is dependent on the catalytic activity of caspases,they mainly act as scaffolding platforms for other signaling proteins in the case of NF-κB signaling.Caspase proteolytic activity,however,counteracts the pro-survival function of NF-κB by cleaving specific signaling molecules.A striking exception is the paracaspase mucosa-associated lymphoid tissue 1(MALT1),whose adaptor and proteolytic activity are both needed to initiate a full blown NF-κB response in antigen-stimulated lymphocytes.Understanding the role of caspases and MALT1 in the regulation of NF-κB signaling is of high interest for therapeutic immunomodulation.

  4. GSH-dependent regulation of Fas-mediated caspase-8 activation by acrolein.

    Hristova, Milena; Heuvelmans, Sjanneke; van der Vliet, Albert


    Activation of the cysteine protease caspase-8 by the death receptor Fas (CD95/APO-1) in B lymphoblastoid SKW6.4 cells or Jurkat T cells is associated with GSH depletion. Conversely, GSH depletion by the aldehyde acrolein (3–30 μM) was associated with inhibition of Fas-induced caspase-8 activation, although GSH depletion by buthionine sulfoximine (BSO) did not affect caspase-8 activation. In contrast to BSO, acrolein caused a loss of caspase-8 cysteine content in association with direct alkyla...

  5. Caspase-3 activation as a bifurcation point between plasticity and cell death

    Shikha Snigdha; Erica D Smith; G Aleph Prieto; Carl W Cotman


    Death-mediating proteases such as caspases and caspase-3 in particular,have been implicated in neurodegenerative processes,aging and Alzheimer's disease.However,emerging evidence suggests that in addition to their classical role in cell death,caspases play a key role in modulating synaptic function.It is remarkable that active caspases-3,which can trigger widespread damage and degeneration,aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death.Here,we evaluate this dichotomy,and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling,able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling.We propose that temporal,spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons.This concept has implications for differential roles of caspase-3 activation across the lifespan.Specifically,we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.

  6. Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism.

    Lu, Alvin; Li, Yang; Schmidt, Florian I; Yin, Qian; Chen, Shuobing; Fu, Tian-Min; Tong, Alexander B; Ploegh, Hidde L; Mao, Youdong; Wu, Hao


    Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar Ki on caspase-1(CARD) polymerization in vitro and inflammasome activation in cells. Whereas caspase-1(CARD) uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament. PMID:27043298

  7. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  8. Expression of Livin, Survivin and Caspase-3 in human brain astrocytoma%Livin、Survivin和Caspase-3在星形细胞瘤中的表达

    赵树鹏; 靳彩玲; 赵新利; 周文科


    目的 探讨Livin、Survivin和Caspase-3在星形细胞瘤中的表达.方法 采用免疫组织化学法检测50例星形细胞瘤标本及10例正常脑组织中Livin、Survivin和Caspase-3的表达,分析Livin、Survivin的表达与Caspase-3表达的关系.结果 Caspase-3在正常脑组织中的阳性表达率显著高于在星形细胞瘤(P<0.05),且在Ⅰ~Ⅱ级星形细胞瘤中的阳性表达率高于Ⅲ~Ⅳ级(P<0.05).Livin和Survivin在星形细胞瘤中的阳性表达率显著高于正常脑组织(P<0.05),且在Ⅲ~Ⅳ级星形细胞瘤中的阳性表达率明显高于Ⅰ~Ⅱ级(P<0.05).星形细胞瘤中Livin和Survivin 的表达与Caspase-3蛋白的表达均呈负相关(r分别为-0.520和-0.360,P<0.05).结论 Livin、Survivin和Caspase-3的表达可能与星形细胞瘤的发生及发展有关.%Objective To explore the expression of Livin, Survivin and Caspase-3 in human brain astrocytoma. Methods The expressions of Livin, Survivin and Caspase-3 in fifty astrocytomas and ten normal brain tissues were detected with immunohistochemical method,and the relationships of Caspase-3 with Livin,Survivin were analyzed. Results The positive rate of Caspase-3 in normal tissue was significantly higher than that in human brain astrocytoma (P <0. 05) ,it was higher in gradeⅠand II than in grade Ⅲ and Ⅳ(P <0. 05) . The positive rates of Livin and Survivin in human brain astrocytoma were significantly higher than those in normal brain tissue(P <0. 05) ,and they were higher in grade Ⅲ and IV than in grade I andII (P <0. 05) . The expressions of Livin and Survivin were negatively correlated with those of Caspase-3 in human brain astro-cytoma( r = - 0.520,r = - 0.360 ,P < 0.05). Conclusion Livin,Survivin and Caspase-3 may play an important role in incidence and development of human brain astrocytoma.

  9. Modeling tumor evolutionary dynamics

    Beatriz eStransky


    Full Text Available Tumorigenesis can be seen as an evolutionary process, in which the transformation of a normal cell into a tumor cell involves a number of limiting genetic and epigenetic events, occurring in a series of discrete stages. However, not all mutations in a cell are directly involved in cancer development and it is likely that most of them (passenger mutations do not contribute in any way to tumorigenesis. Moreover, the process of tumor evolution is punctuated by selection of advantageous (driver mutations and clonal expansions. Regarding these driver mutations, it is uncertain how many limiting events are required and / or sufficient to promote a tumorigenic process or what are the values associated with the adaptive advantage of different driver mutations. In spite of the availability of high-quality cancer data, several assumptions about the mechanistic process of cancer initiation and development remain largely untested, both mathematically and statistically. Here we review the development of mathematical/computational models where some assumptions were tested and discuss the impact of these models to the field of tumor biology.

  10. Evolutionary tracks for Betelgeuse

    Dolan, Michelle M; Lam, Doan Duc; Lan, Nguyen Quynh; Herczeg, Gregory J; Dearborn, David S P


    We have constructed a series of non-rotating quasi-hydrostatic evolutionary models for the M2 Iab supergiant Betelgeuse ($\\alpha~Orionis$). Our models are constrained by multiple values for the observed temperature, luminosity, surface composition and mass loss for this star, along with the parallax distance and high resolution imagery that determines its radius. We have then applied our best-fit models to analyze the observed variations in surface luminosity and the size of detected surface bright spots as the result of up-flowing convective material from regions of high temperature in a surface convective zone. We also attempt to explain the intermittently observed periodic variability in a simple radial linear adiabatic pulsation model. Based upon the best fit to all observed data, we suggest a best progenitor mass estimate of $ 20 ^{+5}_{-3} M_\\odot$ and a current lifetime of $8.0 - 8.5$ Myr based upon the observed ejected mass while on the giant branch.

  11. Industrial Applications of Evolutionary Algorithms

    Sanchez, Ernesto; Tonda, Alberto


    This book is intended as a reference both for experienced users of evolutionary algorithms and for researchers that are beginning to approach these fascinating optimization techniques. Experienced users will find interesting details of real-world problems, and advice on solving issues related to fitness computation, modeling and setting appropriate parameters to reach optimal solutions. Beginners will find a thorough introduction to evolutionary computation, and a complete presentation of all evolutionary algorithms exploited to solve different problems. The book could fill the gap between the

  12. Evolutionary model with Turing machines

    Feverati, Giovanni; Musso, Fabio


    The development of a large noncoding fraction in eukaryotic DNA and the phenomenon of the code bloat in the field of evolutionary computations show a striking similarity. This seems to suggest that (in the presence of mechanisms of code growth) the evolution of a complex code cannot be attained without maintaining a large inactive fraction. To test this hypothesis we performed computer simulations of an evolutionary toy model for Turing machines, studying the relations among fitness and coding versus noncoding ratio while varying mutation and code growth rates. The results suggest that, in our model, having a large reservoir of noncoding states constitutes a great (long term) evolutionary advantage.

  13. Caspase-3 serves as an intracellular immune receptor specific for lipopolysaccharide in oyster Crassostrea gigas.

    Xu, Jiachao; Jiang, Shuai; Li, Yiqun; Li, Meijia; Cheng, Qi; Zhao, Depeng; Yang, Bin; Jia, Zhihao; Wang, Lingling; Song, Linsheng


    Apoptosis is a form of programmed cell death process controlled by a family of cysteine proteases called caspases, which plays a crucial role in the immune system homeostasis. The apoptosis and the detailed regulation mechanism have been well studied in vertebrate, but the information in lower animals, especially invertebrates, is still very limited. In the present study, Caspase-3 in the Pacific oyster Crassostrea gigas (designated CgCaspase-3) was enriched by lipopolysaccharide (LPS) affinity chromatography and further identified by MALDI-TOF/TOF-mass spectrometry. The binding activity of CgCaspase-3 to LPS was confirmed by enzyme-linked immunosorbent assay, and surface plasmon resonance analysis revealed its high binding specificity and moderate binding affinity (KD = 1.08 × 10(-6) M) to LPS. The recombinant CgCaspase-3 exhibited high proteolytic activity to substrate Ac-DEVD-pNA and relatively weak activity to substrate Ac-DMQD-pNA and Ac-VDQQD-pNA. The binding of CgCaspase-3 to LPS significantly inhibited its proteolytic activity toward AC-DEVD-pNA in vitro. The over-expression of CgCaspase-3 leaded to the phosphatidylserine exposure on the external plasma membrane and the cleavage of poly (ADP-ribose) polymerase, which reduced cell viability, and finally induced cell apoptosis. But the cell apoptosis mediated by CgCaspase-3 in vivo was significantly inhibited by the treatment of LPS. These results collectively indicated that CgCaspase-3 could serve as an intracellular LPS receptor, and the interaction of LPS with CgCaspase-3 specifically inhibited the cell apoptosis induced by CgCaspase-3. PMID:26993662

  14. Inhibition of caspase-mediated apoptosis by peroxynitrite in traumatic brain injury.

    Lau, Anthony; Arundine, Mark; Sun, Hong-Shuo; Jones, Michael; Tymianski, Michael


    In traumatic brain injury (TBI), neurons surviving the primary insult may succumb through poorly understood secondary mechanisms. In vitro, cortical neurons exposed to stretch injury exhibited enhanced vulnerability to NMDA, apoptotic-like DNA fragmentation, peroxynitrite (PN) formation, and cytoplasmic cytochrome c accumulation. Surprisingly, caspase-3 activity was undetectable by both immunoblotting and fluorogenic activity assays. Therefore, we hypothesized that PN directly inhibits caspases in these neurons. Consistent with this, stretch injury in cultured neurons elicited tyrosine nitration of procaspase-3, but not caspase-9 or Apaf-1, suggesting a direct interaction of PN with caspase-3. In an ex vivo system, PN inhibited the activity of caspase-3, and this inhibition was reversible with the addition of the sulfhydryl reducing agent dithiothreitol, indicating that PN inhibits caspases by cysteinyl oxidation. Moreover, in cultures, the PN donor 3-morpholinosydnonimine (SIN-1) blocked staurosporine-induced caspase-3 activation and its downstream effects including PARP-1 [poly-(ADP-ribose) polymerase-1] cleavage and phosphotidylserine inversion, suggesting that peroxynitrite can inhibit caspase-3-mediated apoptosis. To examine these mechanisms in vivo, rats were exposed to a lateral fluid percussion injury (FPI). FPI caused increased neuronal protein nitration that colocalized with TUNEL staining, indicating that PN was associated with neurodegeneration. Caspase-3 activity was inhibited in brain lysates harvested after FPI and was restored by adding dithiothreitol. Our data show that caspase-mediated apoptosis is inhibited in neurons subjected to stretch in vitro and to TBI in vivo, mostly because of cysteinyl oxidation of caspase-3 by PN. However, this is insufficient to prevent cell death, indicating that the TBI therapy may, at a minimum, require a combination of both anti-apoptotic and anti-oxidant strategies. PMID:17093075

  15. Both the caspase CSP-1 and a caspase-independent pathway promote programmed cell death in parallel to the canonical pathway for apoptosis in Caenorhabditis elegans.

    Daniel P Denning

    Full Text Available Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3, of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell

  16. Tissue Crowding Induces Caspase-Dependent Competition for Space.

    Levayer, Romain; Dupont, Carole; Moreno, Eduardo


    Regulation of tissue size requires fine tuning at the single-cell level of proliferation rate, cell volume, and cell death. Whereas the adjustment of proliferation and growth has been widely studied [1-5], the contribution of cell death and its adjustment to tissue-scale parameters have been so far much less explored. Recently, it was shown that epithelial cells could be eliminated by live-cell delamination in response to an increase of cell density [6]. Cell delamination was supposed to occur independently of caspase activation and was suggested to be based on a gradual and spontaneous disappearance of junctions in the delaminating cells [6]. Studying the elimination of cells in the midline region of the Drosophila pupal notum, we found that, contrary to what was suggested before, Caspase 3 activation precedes and is required for cell delamination. Yet, using particle image velocimetry, genetics, and laser-induced perturbations, we confirmed [6] that local tissue crowding is necessary and sufficient to drive cell elimination and that cell elimination is independent of known fitness-dependent competition pathways [7-9]. Accordingly, activation of the oncogene Ras in clones was sufficient to compress the neighboring tissue and eliminate cells up to several cell diameters away from the clones. Mechanical stress has been previously proposed to contribute to cell competition [10, 11]. These results provide the first experimental evidences that crowding-induced death could be an alternative mode of super-competition, namely mechanical super-competition, independent of known fitness markers [7-9], that could promote tumor growth. PMID:26898471

  17. P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells

    Qiao CUI; Jing-hua YU; Jin-nan WU; Shin-ichi TASHIRO; Satoshi ONODERA; Mutsuhiko MINAMI; Takashi IKEJIMA


    Aim: To study the caspase-3-independent mechanisms in oridonin-induced MCF-7 human breast cancer cell apoptosis in vitro. Methods: The viability of oridonin-treated MCF-7 cells was measured by MTT (thiazole blue) assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleoso-mal DNA fragmentation was assayed by agarose gel electrophoresis. The apoptotic ratio was determined by lactate dehydrogenase assay. Cell cycle alternation and mitochondrial membrane potential were measured by flow cytometric analysis. Bax, Bcl-2, caspase-3, caspase-9, heat shock protein (Hsp)90, p53, p-p53, p21, Poly (ADP-ribose) polymerase (PARP), and the inhibitor of caspase-activated Dnase (ICAD) protein expressions were detected by Western blot analysis. Results: Oridonin inhibited cell growth in a time- and dose-dependent manner. Cell cycle was altered through the upregulation of p53 and p21 protein expressions. Pan-caspase inhibitor Z-VAD-fmk and calpain inhibitor Ⅱ both decreased cell death ratio. Nucleosomal DNA fragmentation and the downregulation of △ψmit were detected in oridonin-induced MCF-7 cell apoptosis, which was involved in a postmitochondrial caspase-9-dependent pathway. Decreased Bcl-2 and Hsp90 expression levels and increased Bax and p21 expression levels were positively correlated with elevated levels of phosphorylated p53 phosphorylation. Moreover, PARP was partially cleaved by calpain rather than by capase-3. Conclusion: DNA damage provoked alternations in the mitochondrial and caspase-9 pathways as well as p53-mediated cell cycle arrest, but was not related to caspase-3 activity in oridonin-induced MCF-7 cells.

  18. Evolutionary computation for reinforcement learning

    S. Whiteson


    Algorithms for evolutionary computation, which simulate the process of natural selection to solve optimization problems, are an effective tool for discovering high-performing reinforcement-learning policies. Because they can automatically find good representations, handle continuous action spaces, a

  19. Evolutionary Processes and Mental Deficiency

    Spitz, Herman H.


    The author hypothesizes that central nervous system damage of deficiency associated with mental retardation affects primarily those cortical processes which developed at a late stage in man's evolutionary history. (Author)

  20. Molluscan Evolutionary Genomics

    Simison, W. Brian; Boore, Jeffrey L.


    In the last 20 years there have been dramatic advances in techniques of high-throughput DNA sequencing, most recently accelerated by the Human Genome Project, a program that has determined the three billion base pair code on which we are based. Now this tremendous capability is being directed at other genome targets that are being sampled across the broad range of life. This opens up opportunities as never before for evolutionary and organismal biologists to address questions of both processes and patterns of organismal change. We stand at the dawn of a new 'modern synthesis' period, paralleling that of the early 20th century when the fledgling field of genetics first identified the underlying basis for Darwin's theory. We must now unite the efforts of systematists, paleontologists, mathematicians, computer programmers, molecular biologists, developmental biologists, and others in the pursuit of discovering what genomics can teach us about the diversity of life. Genome-level sampling for mollusks to date has mostly been limited to mitochondrial genomes and it is likely that these will continue to provide the best targets for broad phylogenetic sampling in the near future. However, we are just beginning to see an inroad into complete nuclear genome sequencing, with several mollusks and other eutrochozoans having been selected for work about to begin. Here, we provide an overview of the state of molluscan mitochondrial genomics, highlight a few of the discoveries from this research, outline the promise of broadening this dataset, describe upcoming projects to sequence whole mollusk nuclear genomes, and challenge the community to prepare for making the best use of these data.

  1. Lifetime learning in evolutionary robotics

    Ruud, Else-Line Malene


    Inspired by animals ability to learn and adapt to changes in their environment during life, hybrid evolutionary algorithms which include local optimization between generations have been developed and successfully applied in a number of research areas. Despite the possible benefits this kind of algorithm could have in the field of evolutionary robotics, very little research has been done on this topic. This thesis explores the effects of learning used in cooperation with a genetic algorithm t...

  2. Coevolution Evolutionary Algorithm: A Survey

    Jeniefer Kavetha. M


    Evolutionary Computing techniques have become one of the most powerful tools for solving optimization problems and isbased on the mechanisms of natural selection and genetics. In Evolutionary Algorithm, Co-evolution is a natural choice for learning in problem domains where one agent’s behaviour is directly related to the behaviour of other agents. Co-evolution provides a framework to implement search heuristics that are more elaborate than those driving the exploration of the state space in c...

  3. Counterpunishment revisited: an evolutionary approach

    Wolff, Irenaeus


    Evolutionary game theory has shown that in environments characterised by a social-dilemma situation punishment may be an adaptive behaviour. Experimental evidence closely corresponds to this finding but yields contradictory results on the cooperation-enhancing effect of punishment if players are allowed to retaliate against their punishers. The present study sets out to examine the question of whether cooperation will still be part of an evolutionary stable strategy if we allow for counterpun...

  4. Freud: the first evolutionary psychologist?

    LeCroy, D


    An evolutionary perspective on attachment theory and psychoanalytic theory brings these two fields together in interesting ways. Application of the evolutionary principle of parent-offspring conflict to attachment theory suggests that attachment styles represent context-sensitive, evolved (adaptive) behaviors. In addition, an emphasis on offspring counter-strategies to adult reproductive strategies leads to consideration of attachment styles as overt manifestations of psychodynamic mediating processes, including the defense mechanisms of repression and reaction formation. PMID:10818628

  5. Evolutionary Explanations of Eating Disorders

    Igor Kardum; Asmir Gračanin; Jasna Hudek-Knežević


    This article reviews several most important evolutionary mechanisms that underlie eating disorders. The first part clarifies evolutionary foundations of mental disorders and various mechanisms leading to their development. In the second part selective pressures and evolved adaptations causing contemporary epidemic of obesity as well as differences in dietary regimes and life-style between modern humans and their ancestors are described. Concerning eating disorders, a number of current evoluti...

  6. How competition affects evolutionary rescue

    Osmond, Matthew Miles; de Mazancourt, Claire


    Populations facing novel environments can persist by adapting. In nature, the ability to adapt and persist will depend on interactions between coexisting individuals. Here we use an adaptive dynamic model to assess how the potential for evolutionary rescue is affected by intra- and interspecific competition. Intraspecific competition (negative density-dependence) lowers abundance, which decreases the supply rate of beneficial mutations, hindering evolutionary rescue. On the other hand, inters...

  7. Evolutionary economics and regional policy

    Lambooy, Jan G.; Boschma, Ron


    The principal objective of this paper is to formulate some possible links between evolutionary economics and regional policy, a topic that has not (yet) been covered by the literature. We firstly give a brief overview of some issues of regional policy, conceived as a strategy to influence the spatial matrix of economic development. Then, we outline what we take to be the essential arguments and components of evolutionary economics. More in particular, we focus attention on the economic founda...

  8. Behaviour Trees for Evolutionary Robotics

    Scheper, Kirk Y. W.; Tijmons, Sjoerd; de Visser, Coen C.; de Croon, Guido C. H. E.


    Evolutionary Robotics allows robots with limited sensors and processing to tackle complex tasks by means of sensory-motor coordination. In this paper we show the first application of the Behaviour Tree framework to a real robotic platform using the Evolutionary Robotics methodology. This framework is used to improve the intelligibility of the emergent robotic behaviour as compared to the traditional Neural Network formulation. As a result, the behaviour is easier to comprehend and manually ad...

  9. Evolutionary Algorithms and Dynamic Programming

    Doerr, Benjamin; Eremeev, Anton; Neumann, Frank; Theile, Madeleine; Thyssen, Christian


    Recently, it has been proven that evolutionary algorithms produce good results for a wide range of combinatorial optimization problems. Some of the considered problems are tackled by evolutionary algorithms that use a representation which enables them to construct solutions in a dynamic programming fashion. We take a general approach and relate the construction of such algorithms to the development of algorithms using dynamic programming techniques. Thereby, we give general guidelines on how ...

  10. Evolutionary Algorithms in Astronautic Applications

    Maiwald, Volker


    Evolutionary algorithms (EA) are a computation tool that utilizes biological principles found in the evolution theory. One major difference to other optimization methods is the fact that a large group of solutions is evaluated, not a single one. Combination of various solutions from such a group, called population, allows improvement of the solutions. Overall several terms in usage in the field of evolutionary algorithms have their origin in genetics or biology, especially the ...

  11. Evolutionary Algorithms for Reinforcement Learning

    Grefenstette, J. J.; Moriarty, D. E.; Schultz, A.C.


    There are two distinct approaches to solving reinforcement learning problems, namely, searching in value function space and searching in policy space. Temporal difference methods and evolutionary algorithms are well-known examples of these approaches. Kaelbling, Littman and Moore recently provided an informative survey of temporal difference methods. This article focuses on the application of evolutionary algorithms to the reinforcement learning problem, emphasizing alternative policy represe...

  12. Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection

    Tamayev Robert


    Full Text Available Abstract Background Mutations in either Aβ Precursor protein (APP or genes that regulate APP processing, such as BRI2/ITM2B and PSEN1/PSEN2, cause familial dementias. Although dementias due to APP/PSEN1/PSEN2 mutations are classified as familial Alzheimer disease (FAD and those due to mutations in BRI2/ITM2B as British and Danish dementias (FBD, FDD, data suggest that these diseases have a common pathogenesis involving toxic APP metabolites. It was previously shown that FAD mutations in APP and PSENs promote activation of caspases leading to the hypothesis that aberrant caspase activation could participate in AD pathogenesis. Results Here, we tested whether a similar mechanism applies to the Danish BRI2/ITM2B mutation. We have generated a genetically congruous mouse model of FDD, called FDDKI, which presents memory and synaptic plasticity deficits. We found that caspase-9 is activated in hippocampal synaptic fractions of FDDKI mice and inhibition of caspase-9 activity rescues both synaptic plasticity and memory deficits. Conclusion These data directly implicate caspase-9 in the pathogenesis of Danish dementia and suggest that reducing caspase-9 activity is a valid therapeutic approach to treating human dementias.

  13. Caspase-3和bax在视网膜母细胞瘤中的表达%Expression of caspase-3 and bax gene protein in retinoblastoma

    孙红; 惠延年; 王立勤; 马吉献


    目的: 观察凋亡及凋亡调控基因caspase-3/bax在视网膜母细胞瘤(retinoblastoma, RB)中的表达及与凋亡的相关性. 方法: 收集35例RB标本,对其分别进行caspase-3和bax免疫组织化学染色,观察表达情况及染色强度. 结果: Caspase-3及bax在未分化型(n=15)分别有较好的表达(11/12例),caspase-3及bax在分化型(n=20)中也有较好的表达(17/18例). 正常视网膜组织中无caspase-3及bax的表达. 结论: 凋亡在RB中是存在的,caspase-3及bax在RB的发生发展中起重要作用.

  14. Caspase-1 and 3 Inhibiting Drimane Sesquiterpenoids from the Extremophilic Fungus, Penicillium solitum

    Stierle, Donald B.; Stierle, Andrea A.; Girtsman, Teri; McIntyre, Kyle; Nichols, Jesse


    Two new drimane sesquiterpene lactones and one new tricarboxylic acid derivative were isolated from the Berkeley Pit extremophilic fungus Penicillium solitum. The structures of these compounds were deduced by spectroscopic analysis. Berkedrimanes A and B inhibited the signal transduction enzymes caspase-1 and caspase-3 and mitigated the production of interleukin 1-β in the induced THP-1 (promonocytic leukemia cell line) assay.

  15. Two-Photon Enzymatic Probes Visualizing Sub-cellular/Deep-brain Caspase Activities in Neurodegenerative Models.

    Qian, Linghui; Zhang, Cheng-Wu; Mao, Yanli; Li, Lin; Gao, Nengyue; Lim, Kah-Leong; Xu, Qing-Hua; Yao, Shao Q


    Caspases work as a double-edged sword in maintaining cell homeostasis. Highly regulated caspase activities are essential during animal development, but dysregulation might lead to different diseases, e.g. extreme caspase activation is known to promote neurodegeneration. At present, visualization of caspase activation has mostly remained at the cellular level, in part due to a lack of cell-permeable imaging probes capable of direct, real-time investigations of endogenous caspase activities in deep tissues. Herein, we report a suite of two-photon, small molecule/peptide probes which enable sensitive and dynamic imaging of individual caspase activities in neurodegenerative models under physiological conditions. With no apparent toxicity and the ability of imaging endogenous caspases both in different subcellular organelles of mammalian cells and in brain tissues, these probes serve as complementary tools to conventional histological analysis. They should facilitate future explorations of caspases at molecular, cellular and organism levels and inspire development of novel two-photon probes against other enzymes. PMID:27210613

  16. Caspase-1 and IL-1β processing in a teleost fish.

    Marta I R Reis

    Full Text Available Interleukine-1β (IL-1β is the most studied pro-inflammatory cytokine, playing a central role in the generation of systemic and local responses to infection, injury, and immunological challenges. In mammals, IL-1β is synthesized as an inactive 31 kDa precursor that is cleaved by caspase-1 generating a 17.5 kDa secreted active mature form. The caspase-1 cleavage site strictly conserved in all mammalian IL-1β sequences is absent in IL-1β sequences reported for non-mammalian vertebrates. Recently, fish caspase-1 orthologues have been identified in sea bass (Dicentrarchus labrax and sea bream (Sparus aurata but very little is known regarding their processing and activity. In this work it is shown that sea bass caspase-1 auto-processing is similar to that of the human enzyme, resulting in active p24/p10 and p20/p10 heterodimers. Moreover, the presence of alternatively spliced variants of caspase-1 in sea bass is reported. The existence of caspase-1 isoforms in fish and in mammals suggests that they have been evolutionarily maintained and therefore are likely to play a regulatory role in the inflammatory response, as shown for other caspases. Finally, it is shown that sea bass and avian IL-1β are specifically cleaved by caspase-1 at different but phylogenetically conserved aspartates, distinct from the cleavage site of mammalian IL-1β.

  17. Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.

    Machado, M V; Michelotti, G A; Jewell, M L; Pereira, T A; Xie, G; Premont, R T; Diehl, A M


    Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro-inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic fatty liver disease), insulin resistance and the metabolic syndrome. Recently, caspase-2 was linked to lipoapoptosis, so we hypothesized that caspase-2 might be a critical determinant of metabolic syndrome pathogenesis. Caspase-2-deficient and wild-type mice were fed a Western diet (high-fat diet, enriched with saturated fatty acids and 0.2% cholesterol, supplemented with fructose and glucose in the drinking water) for 16 weeks. Metabolic and hepatic outcomes were evaluated. In vitro studies assessed the role of caspase-2 in adipose tissue proliferative properties and susceptibility for lipoapoptosis. Caspase-2-deficient mice fed a Western diet were protected from abdominal fat deposition, diabetes mellitus, dyslipidemia and hepatic steatosis. Adipose tissue in caspase-2-deficient mice was more proliferative, upregulated mitochondrial uncoupling proteins consistent with browning, and was resistant to cell hypertrophy and cell death. The liver was protected from steatohepatitis through a decrease in circulating fatty acids and more efficient hepatic fat metabolism, and from fibrosis as a consequence of reduced fibrogenic stimuli from fewer lipotoxic hepatocytes. Caspase-2 deficiency protected mice from diet-induced obesity, metabolic syndrome and nonalcoholic fatty liver disease. Further studies are necessary to assess caspase-2 as a therapeutic target for those conditions. PMID:26890135

  18. Neutronic and thermalhydraulic aspects

    Precise computation of neutron flux in the core of a nuclear reactor represents one of the basic aspects of reactor design and operation. Neutron flux is computed by solving Boltzmann's linear equation. Anyway, the direct solution of the equation involves too great a number of operations for practical application, leading up to TeraFlops or even PetaFlops supercomputing capabilities. Physical and mathematical models are then required to handle the extensive variety of configurations encountered. Numerical methods must be adapted to the rapid evolution of computer power, as also computer architecture: sequential, vector or parallel. Physical and mathematical models must allow for very fast estimation for online control and monitoring, adequate quantification for industrial studies and high-precision, best estimate computations. Coupling of neutronics to mechanics and two-phase flow thermohydraulics must be implemented in order to improve the accuracy in best-estimate computation schemes and to take into account the transient behaviour of the plant during normal operation or incidents. In this field of continuous improvement, the new methods applied in Reactor Physics lead obviously to good results and provide the improvements required in the future for the needs of efficiency, safety and advanced fuel cycle. This trend and the ''evolutionary'' implementation in large and modular software systems will be illustrated by the example of the SAPHYR system. (authors). 3 tabs

  19. A quantitative method for the specific assessment of caspase-6 activity in cell culture

    Ehrnhoefer, Dagmar E; Skotte, Niels H; Savill, Jane;


    are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples. Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly...... specific for caspase-6 cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts. The method is more sensitive than......Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods...

  20. Deficiency of caspase 3 in tumor xenograft impairs therapeutic effect of measles virus Edmoston strain.

    Wang, Biao; Yan, Xu; Guo, Qingguo; Li, Yan; Zhang, Haiyan; Xie, Ji Sheng; Meng, Xin


    The oncolytic measles virus Edmonston (MV-Edm) strain shows considerable oncolytic activity against a variety of human tumors. In this study, we report MV-Edm is able to trigger apoptosis pathways in infected tumor cells and elucidate the roles of cellular apoptosis in the whole oncolytic process. We also show that activated caspase 3, a key executioner of apoptosis, plays key roles in the oncolytic virotherapy. Activated caspase 3 can accelerate viral replication in cervical cancer cells and enhance the killing effects of the virus. Deficiency of caspase 3 either in tumor cells or in tumor xenograft significantly desensitized tumor to oncolysis with MV-Edm. In the infected cells, caspase 3 regulates interferon α release, which can inhibit viral replication in neighboring tumor cells. We propose that caspase-3 activation enhances the oncolytic effects of MV-Edm, thus inhibiting tumor growth in mice. PMID:25909216

  1. Retinal Cell Death Caused by Sodium Iodate Involves Multiple Caspase-Dependent and Caspase-Independent Cell-Death Pathways

    Jasmin Balmer


    Full Text Available Herein, we have investigated retinal cell-death pathways in response to the retina toxin sodium iodate (NaIO3 both in vivo and in vitro. C57/BL6 mice were treated with a single intravenous injection of NaIO3 (35 mg/kg. Morphological changes in the retina post NaIO3 injection in comparison to untreated controls were assessed using electron microscopy. Cell death was determined by TdT-mediated dUTP-biotin nick end labeling (TUNEL staining. The activation of caspases and calpain was measured using immunohistochemistry. Additionally, cytotoxicity and apoptosis in retinal pigment epithelial (RPE cells, primary retinal cells, and the cone photoreceptor (PRC cell line 661W were assessed in vitro after NaIO3 treatment using the ApoToxGlo™ assay. The 7-AAD/Annexin-V staining was performed and necrostatin (Nec-1 was administered to the NaIO3-treated cells to confirm the results. In vivo, degenerating RPE cells displayed a rounded shape and retracted microvilli, whereas PRCs featured apoptotic nuclei. Caspase and calpain activity was significantly upregulated in retinal sections and protein samples from NaIO3-treated animals. In vitro, NaIO3 induced necrosis in RPE cells and apoptosis in PRCs. Furthermore, Nec-1 significantly decreased NaIO3-induced RPE cell death, but had no rescue effect on treated PRCs. In summary, several different cell-death pathways are activated in retinal cells as a result of NaIO3.

  2. Stochastic Evolutionary Algorithms for Planning Robot Paths

    Fink, Wolfgang; Aghazarian, Hrand; Huntsberger, Terrance; Terrile, Richard


    A computer program implements stochastic evolutionary algorithms for planning and optimizing collision-free paths for robots and their jointed limbs. Stochastic evolutionary algorithms can be made to produce acceptably close approximations to exact, optimal solutions for path-planning problems while often demanding much less computation than do exhaustive-search and deterministic inverse-kinematics algorithms that have been used previously for this purpose. Hence, the present software is better suited for application aboard robots having limited computing capabilities (see figure). The stochastic aspect lies in the use of simulated annealing to (1) prevent trapping of an optimization algorithm in local minima of an energy-like error measure by which the fitness of a trial solution is evaluated while (2) ensuring that the entire multidimensional configuration and parameter space of the path-planning problem is sampled efficiently with respect to both robot joint angles and computation time. Simulated annealing is an established technique for avoiding local minima in multidimensional optimization problems, but has not, until now, been applied to planning collision-free robot paths by use of low-power computers.

  3. Caspase inhibitors of the P35 family are more active when purified from yeast than bacteria.

    Ingo L Brand

    Full Text Available Many insect viruses express caspase inhibitors of the P35 superfamily, which prevent defensive host apoptosis to enable viral propagation. The prototypical P35 family member, AcP35 from Autographa californica M nucleopolyhedrovirus, has been extensively studied. Bacterially purified AcP35 has been previously shown to inhibit caspases from insect, mammalian and nematode species. This inhibition occurs via a pseudosubstrate mechanism involving caspase-mediated cleavage of a "reactive site loop" within the P35 protein, which ultimately leaves cleaved P35 covalently bound to the caspase's active site. We observed that AcP35 purifed from Saccharomyces cerevisae inhibited caspase activity more efficiently than AcP35 purified from Escherichia coli. This differential potency was more dramatic for another P35 family member, MaviP35, which inhibited human caspase 3 almost 300-fold more potently when purified from yeast than bacteria. Biophysical assays revealed that MaviP35 proteins produced in bacteria and yeast had similar primary and secondary structures. However, bacterially produced MaviP35 possessed greater thermal stability and propensity to form higher order oligomers than its counterpart purified from yeast. Caspase 3 could process yeast-purified MaviP35, but failed to detectably cleave bacterially purified MaviP35. These data suggest that bacterially produced P35 proteins adopt subtly different conformations from their yeast-expressed counterparts, which hinder caspase access to the reactive site loop to reduce the potency of caspase inhibition, and promote aggregation. These data highlight the differential caspase inhibition by recombinant P35 proteins purified from different sources, and caution that analyses of bacterially produced P35 family members (and perhaps other types of proteins may underestimate their activity.

  4. Testosterone undecanoate and depo medroxyprogesterone acetate induced azoospermia through increased expression of spermatogenic cell caspase 3

    Nukman Moeloek


    Full Text Available The administration of a combination of testosterone undecanoate (TU, a long-acting androgen and depo-medroxyprogesterone acetate (DMPA were investigated in term of suppression of rat sperm concentration in vivo to azoospermia through increasing activity of spermatogenic cell caspase 3. Adult Sprague Dawley rats received TU and DMPA of 2.5 mg and 1.25 mg, respectively, a regimen known to rapidly reduce intra testicular testosterone and to produce azoospermia within 12 weeks. Caspase 3 positive sperm cells increased compared with control levels during 6 weeks post-injection and increased further through 60 weeks. Immunohistochemistry for caspase 3 revealed that spermatocytes represented the predominant caspase 3 positive germ cells. Modest immunoreactivity for caspase-3 was localized to nuclear region of the germ cells of control and treated testes. Immunohistochemistry study revealed significantly increased caspase-3 expression in nuclei of germ cells during administration of TU+DMPA to rats. Additionally, the caspase 3 content was significantly increased in germ cells during rats were administered TU+DMPA (453.90±84.88 cells/200 seminiferous tubules and caspase 3 significant increase in immunoreactivity was localized to the nuclei of spermatogonia, spermatocytes, and spermatids. Taken together, these results indicated that azoospermia due to reduced intratesticular testosterone concentration was caspase-3 activation dependent and suggested that the increase in active caspase-3 in the nucleus may be involved in the induction of decreased sperm production. (Med J Indones 2008; 17: 149-56Keywords: TU, DMPA, sperm concentration, germ cells

  5. Novel HTS strategy identifies TRAIL-sensitizing compounds acting specifically through the caspase-8 apoptotic axis.

    Darren Finlay

    Full Text Available Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7 compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be "weeded out" in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries.

  6. Transition matrix model for evolutionary game dynamics

    Ermentrout, G. Bard; Griffin, Christopher; Belmonte, Andrew


    We study an evolutionary game model based on a transition matrix approach, in which the total change in the proportion of a population playing a given strategy is summed directly over contributions from all other strategies. This general approach combines aspects of the traditional replicator model, such as preserving unpopulated strategies, with mutation-type dynamics, which allow for nonzero switching to unpopulated strategies, in terms of a single transition function. Under certain conditions, this model yields an endemic population playing non-Nash-equilibrium strategies. In addition, a Hopf bifurcation with a limit cycle may occur in the generalized rock-scissors-paper game, unlike the replicator equation. Nonetheless, many of the Folk Theorem results are shown to hold for this model.

  7. Technological readiness of evolutionary water cooled reactors

    Nuclear energy has evolved to a mature industry that supplies over 16% of the world's electricity, and it represents an important option for meeting the global energy demands of the coming century in an environmentally acceptable manner. New, evolutionary water cooled reactor designs that build on successful performance of predecessors have been developed; these designs have generally been guided by wishes to reduce cost, to improve availability and reliability, and to meet increasingly stringent safety objectives. These three aspects are important factors in what has been called technological readiness for an expanded deployment of nuclear power; a major increase in utilization of nuclear power will only occur if it is economically competitive, and meets safety expectations. To this end, the industry will also have to maintain or improve the public perception of nuclear power as a benign, economical and reliable energy source. (author)

  8. Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

    Flavell Richard A


    Full Text Available Abstract We recently demonstrated that caspase-3 is important for apoptosis during spontaneous involution of the corpus luteum (CL. These studies tested if prostaglandin F2α (PGF2α or FAS regulated luteal regression, utilize a caspase-3 dependent pathway to execute luteal cell apoptosis, and if the two receptors work via independent or potentially shared intracellular signaling components/pathways to activate caspase-3. Wild-type (WT or caspase-3 deficient female mice, 25–26 days old, were given 10 IU equine chorionic gonadotropin (eCG intraperitoneally (IP followed by 10 IU human chorionic gonadotropin (hCG IP 46 h later to synchronize ovulation. The animals were then injected with IgG (2 micrograms, i.v., the FAS-activating antibody Jo2 (2 micrograms, i.v., or PGF2α (10 micrograms, i.p. at 24 or 48 h post-ovulation. Ovaries from each group were collected 8 h later for assessment of active caspase-3 enzyme and apoptosis (measured by the TUNEL assay in the CL. Regardless of genotype or treatment, CL in ovaries collected from mice injected 24 h after ovulation showed no evidence of active caspase-3 or apoptosis. However, PGF2α or Jo2 at 48 h post-ovulation and collected 8 h later induced caspase-3 activation in 13.2 ± 1.8% and 13.7 ± 2.2 % of the cells, respectively and resulted in 16.35 ± 0.7% (PGF2α and 14.3 ± 2.5% TUNEL-positive cells when compared to 1.48 ± 0.8% of cells CL in IgG treated controls. In contrast, CL in ovaries collected from caspase-3 deficient mice whether treated with PGF2α , Jo2, or control IgG at 48 h post-ovulation showed little evidence of active caspase-3 or apoptosis. CL of WT mice treated with Jo2 at 48 h post-ovulation had an 8-fold increase in the activity of caspase-8, an activator of caspase-3 that is coupled to the FAS death receptor. Somewhat unexpectedly, however, treatment of WT mice with PGF2α at 48 h post-ovulation resulted in a 22-fold increase in caspase-8 activity in the CL, despite the fact

  9. When Beauty Is Skin Deep: Regulation of the Wound Response by Caspase-8, RIPK3, and the Inflammasome.

    Vince, James E


    Caspase-8 downregulation is observed in the epidermis of wounded skin, whereas permanent epidermal caspase-8 deletion causes chronic skin inflammation, suggesting that caspase-8 is a critical regulator of skin homeostasis and, possibly, the wound response. In this issue, Lee et al. document how epidermal caspase-8 deletion, or cutaneous wounding, results in increased NF-κB activation to drive keratinocyte caspase-1 expression and subsequent secretion of the pro-inflammatory cytokines, IL-1β and IL-1α. Consequently, loss of NF-κB activity, caspase-1, or the IL-1 receptor delays wound healing. Previous studies have documented how chronic skin inflammation in caspase-8-deficient mice is rescued by RIPK3 co-deletion. Therefore, targeting caspase-1, IL-1, or RIPK3 itself may benefit treatment of chronic inflammatory skin diseases, or where an inappropriate inflammatory response proves detrimental to wound healing, such as in type 2 diabetes. PMID:26174535

  10. The major synthetic evolutionary transitions

    Solé, Ricard


    Evolution is marked by well-defined events involving profound innovations that are known as ‘major evolutionary transitions'. They involve the integration of autonomous elements into a new, higher-level organization whereby the former isolated units interact in novel ways, losing their original autonomy. All major transitions, which include the origin of life, cells, multicellular systems, societies or language (among other examples), took place millions of years ago. Are these transitions unique, rare events? Have they instead universal traits that make them almost inevitable when the right pieces are in place? Are there general laws of evolutionary innovation? In order to approach this problem under a novel perspective, we argue that a parallel class of evolutionary transitions can be explored involving the use of artificial evolutionary experiments where alternative paths to innovation can be explored. These ‘synthetic’ transitions include, for example, the artificial evolution of multicellular systems or the emergence of language in evolved communicating robots. These alternative scenarios could help us to understand the underlying laws that predate the rise of major innovations and the possibility for general laws of evolved complexity. Several key examples and theoretical approaches are summarized and future challenges are outlined. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431528